linoleic-acid and Neoplasms

Human aldo-keto reductase family 1 member C3 (AKR1C3) is known as a hormone activity regulator and prostaglandin F (PGF) synthase that regulates the occupancy of hormone receptors and cell proliferation. Because of the overexpression in metabolic diseases and various hormone-dependent and -independent carcinomas, as well as the emergence of clinical drug resistance, an increasing number of studies have investigated AKR1C3 inhibitors. Here, we briefly review the physiological and pathological function of AKR1C3 and then summarize the recent development of selective AKR1C3 inhibitors. We propose our viewpoints on the current problems associated with AKR1C3 inhibitors with the aim of providing a reference for future drug discovery and potential therapeutic perspectives on novel, potent, selective AKR1C3 inhibitors.

Topics: Aldo-Keto Reductase Family 1 Member C3; Antineoplastic Agents; Binding Sites; Cell Proliferation; Clinical Trials as Topic; Drug Development; Drug Resistance, Neoplasm; Humans; Models, Molecular; Molecular Structure; Neoplasms; Treatment Outcome

Lipoxygenases (LOXs) are enzymes which found in organisms that catalyze the peroxidation of polyunsaturated fatty acids (Arachidonic acid, Linoleic acid). The key role of the mentioned enzymes and their metabolites in formation of sensitivities, inflammations, many of cancers (prostate, breast, etc), obesity, diabetes and atherosclerosis had been demonstrated. This review aimed to focus on research findings introducing proved LOXs (5/12/15-LOX) inhibitors, which have been involved in in vivo studies, and discuss on their sources, chemical structures and medicinal applications. By this subject selection, we would introduce the possible LOXs inhibitors (5/12/15-LOX) with special physiological and metabolic levels and open a vision in molecular target selection for the readers.

Topics: Animals; Arachidonic Acid; Humans; Linoleic Acid; Lipoxygenase Inhibitors; Lipoxygenases; Neoplasms

Current evidence on associations between intakes of linoleic acid (LA), the predominant n-6 (ω-6) fatty acid, and mortality is inconsistent and has not been summarized by a systematic review and meta-analysis.. The aim was to perform a systematic review and meta-analysis of prospective cohort studies to examine associations between LA intake and mortality.. We conducted a comprehensive search of MEDLINE and EMBASE databases through 31 July 2019 for prospective cohort studies reporting associations of LA (assessed by dietary surveys and/or LA concentrations in adipose tissue or blood compartments) with mortality from all causes, cardiovascular disease (CVD), and cancer. Multivariable-adjusted RRs were pooled using random-effects meta-analysis.. Thirty-eight studies reporting 44 prospective cohorts were identified; these included 811,069 participants with dietary intake assessment (170,076 all-cause, 50,786 CVD, and 59,684 cancer deaths) and 65,411 participants with biomarker measurements (9758 all-cause, 6492 CVD, and 1719 cancer deaths). Pooled RRs comparing extreme categories of dietary LA intake (high vs low) were 0.87 (95% CI: 0.81, 0.94; I2 = 67.9%) for total mortality, 0.87 (95% CI: 0.82, 0.92; I2 = 3.7%) for CVD mortality, and 0.89 (95% CI: 0.85, 0.93; I2 = 0%) for cancer mortality. Pooled RRs for each SD increment in LA concentrations in adipose tissue/blood compartments were 0.91 (95% CI: 0.87, 0.95; I2 = 64.1%) for total mortality, 0.89 (95% CI: 0.85, 0.94; I2 = 28.9%) for CVD mortality, and 0.91 (95% CI: 0.84, 0.98; I2 = 26.3%) for cancer mortality. Meta-regressions suggested baseline age and dietary assessment methods as potential sources of heterogeneity for the association between LA and total mortality.. In prospective cohort studies, higher LA intake, assessed by dietary surveys or biomarkers, was associated with a modestly lower risk of mortality from all causes, CVD, and cancer. These data support the potential long-term benefits of PUFA intake in lowering the risk of CVD and premature death.

Topics: Adult; Aged; Aged, 80 and over; Cardiovascular Diseases; Fatty Acids, Omega-6; Female; Humans; Linoleic Acid; Male; Middle Aged; Neoplasms; Prospective Studies; Randomized Controlled Trials as Topic; Young Adult

Topics: Animals; Carcinogenesis; Cytochrome P-450 Enzyme System; Humans; Linoleic Acid; Neoplasms; Oxylipins

Previous studies on the association between polyunsaturated fatty acids (PUFAs) and cancer have focused on n-3 PUFAs. To investigate the association between intake or blood levels of n-6 PUFAs and cancer, we searched the PubMed and Embase databases up to March 2020 and conducted a meta-analysis. A total of 70 articles were identified. High blood levels of n-6 PUFAs were associated with an 8% lower risk of all cancers (relative risk (RR) = 0.92; 95% confidence interval (CI): 0.86-0.98) compared to low blood levels of n-6 PUFAs. In the subgroup analyses by cancer site, type of n-6 PUFAs, and sex, the inverse associations were strong for breast cancer (RR = 0.87; 95% CI: 0.77-0.98), linoleic acid (LA) (RR = 0.91; 95% CI: 0.82-1.00), and women (RR = 0.88; 95% CI: 0.79-0.97). In the dose-response analysis, a 2% and 3% decrease in the risk of cancer was observed with a 5% increase in blood levels of n-6 PUFAs and LA, respectively. Thus, there was no significant association between n-6 PUFA intake and the risk of cancer. The pooled RR of cancer for the highest versus lowest category of n-6 PUFA intake was 1.02 (95% CI: 0.99-1.05). Evidence from prospective studies indicated that intake of n-6 PUFAs was not significantly associated with risk of cancer, but blood levels of n-6 PUFAs were inversely associated with risk of cancer.

Topics: Dietary Supplements; Eating; Fatty Acids, Omega-6; Female; Humans; Linoleic Acid; Male; Neoplasms; Nutritional Physiological Phenomena; Prospective Studies; Risk

Obesity and its comorbidities, including type 2 diabetes and cardiovascular disease, are straining our healthcare system, necessitating the development of novel strategies for weight loss. Lifestyle modifications, such as exercise and caloric restriction, have proven effective against obesity in the short term, yet obesity persists because of the high predilection for weight regain. Therefore, alternative approaches to achieve long term sustainable weight loss are urgently needed. Conjugated linoleic acid (CLA), a fatty acid found naturally in ruminant animal food products, has been identified as a potential anti-obesogenic agent, with substantial efficacy in mice, and modest efficacy in obese human populations. Originally described as an anti-carcinogenic fatty acid, in addition to its anti-obesogenic effects, CLA has now been shown to possess anti-atherosclerotic properties. This review summarizes the pre-clinical and human studies conducted using CLA to date, which collectively suggest that CLA has efficacy against cancer, obesity, and atherosclerosis. In addition, the potential mechanisms for the many integrative physiological effects of CLA supplementation will be discussed in detail, including an introduction to the gut microbiota as a potential mediator of CLA effects on obesity and atherosclerosis.

Topics: Atherosclerosis; Humans; Linoleic Acid; Neoplasms; Obesity

Dietary fat quality, especially the intake of specific types of fatty acids, impacts the risk of many chronic diseases, including cardiovascular diseases, certain cancers and type 2 diabetes (T2DM). A recent pooled analysis involving 20 studies from around the world revealed that higher linoleic acid (18:2n-6 LA) biomarker is associated with dose-dependent decreases in the incidence of T2DM. This latest study corroborates earlier cross-sectional studies and intervention trials showing that biomarkers of LA intake are associated with reduced risk of T2DM and better glycemic control and/or insulin sensitivity. This review highlights key clinical trials that have evaluated the role of LA in glycemia and the related condition, insulin sensitivity.

Topics: Blood Glucose; Cardiovascular Diseases; Clinical Trials as Topic; Diabetes Mellitus, Type 2; Dietary Fats; Humans; Insulin Resistance; Linoleic Acid; Neoplasms; Risk

Dietary fatty acids are associated with the development of many chronic diseases, such as obesity, diabetes, cardiovascular disease, metabolic syndrome, and several cancers. This review explores the literature surrounding the combined and individual roles of n-6 PUFAs linoleic acid (LA) and arachidonic acid (AA) as they relate to immune and inflammatory response, cardiovascular health, liver health, and cancer. The evidence suggests that a pro-inflammatory view of LA and AA may be over simplified. Overall, this review highlights gaps in our understanding of the biological roles of LA, AA and their complex relationship with n-3 PUFA and the need for future studies that examine the roles of individual fatty acids, rather than groups.

Topics: Animals; Arachidonic Acid; Cardiovascular Diseases; Dietary Fats, Unsaturated; Gene Knockout Techniques; Humans; Inflammation; Linoleic Acid; Linoleoyl-CoA Desaturase; Liver Diseases; Neoplasms

Linoleic acid (LA) is a major constituent of low-density lipoproteins. An essential fatty acid, LA is a polyunsaturated fatty acid, which is oxidised by endogenous enzymes and reactive oxygen species in the circulation. Increased levels of low-density lipoproteins coupled with oxidative stress and lack of antioxidants drive the oxidative processes. This results in synthesis of a range of oxidised derivatives, which play a vital role in regulation of inflammatory processes. The derivatives of LA include, hydroxyoctadecadienoic acids, oxo-​octadecadienoic acids, epoxy octadecadecenoic acid and epoxy-keto-octadecenoic acids. In this review, we examine the role of LA derivatives and their actions on regulation of inflammation relevant to metabolic processes associated with atherogenesis and cancer. The processes affected by LA derivatives include, alteration of airway smooth muscles and vascular wall, affecting sensitivity to pain, and regulating endogenous steroid hormones associated with metabolic syndrome. LA derivatives alter cell adhesion molecules, this initial step, is pivotal in regulating inflammatory processes involving transcription factor peroxisome proliferator-activated receptor pathways, thus, leading to alteration of metabolic processes. The derivatives are known to elicit pleiotropic effects that are either beneficial or detrimental in nature hence making it difficult to determine the exact role of these derivatives in the progress of an assumed target disorder. The key may lie in understanding the role of these derivatives at various stages of development of a disorder. Novel pharmacological approaches in altering the synthesis or introduction of synthesised LA derivatives could possibly help drive processes that could regulate inflammation in a beneficial manner. Chemical Compounds: Linoleic acid (PubChem CID: 5280450), 9- hydroxyoctadecadienoic acid (PubChem CID: 5312830), 13- hydroxyoctadecadienoic acid (PubChem CID: 6443013), 9-oxo-​octadecadienoic acid (PubChem CID: 3083831), 13-oxo-​octadecadienoic acid (PubChem CID: 4163990), 9,10-epoxy-12-octadecenoate (PubChem CID: 5283018), 12,13-epoxy-9-keto-10- trans -octadecenoic acid (PubChem CID: 53394018), Pioglitazone (PubChem CID: 4829).

Topics: Animals; Fatty Acids, Unsaturated; Humans; Inflammation; Linoleic Acid; Metabolic Syndrome; Neoplasms; Oxidation-Reduction

15-Lipoxygenases (15-LOXes) are a family of iron-containing proteins that have the capability for unsaturated fatty acid peroxidation in animals and plants. Two types of the enzyme, 15-LOX-1 and 15-LOX-2, have been recognized in mammals to have different abilities in the peroxidation of arachidonic acid and linoleic acid. In mammalians, the critical role of the mentioned enzymes and their metabolites, hydroxyoctadecadienoic acid (HODE), lipoxins and eoxins, in the formation of inflammation, sensitivities, atherosclerosis and some cancers has been demonstrated.. This article reviews relevant publications and patents on 15-LOX inhibitors from the points of view of synthesis and biological activities. Herein, based on the chemical structure and pharmacophore moiety, 15-LOX inhibitors are categorized into heterocyclic, phenolic, allyl and allyloxy derivatives.. It is noteworthy that to date no pharmaceutical product from 15-LOX inhibitors has been approved for therapeutic usage. Recently, the role of 15-LOX-1 in obesity, by directly relating 15-LOX-1 expression with the proliferation and hypertrophy of adipose cells, has been reported. Based on the role 15-LOX plays in promoting cancer by amplifying PPARγ transcription activity, however, it can be claimed that 15-LOX inhibitors will be deemed suitable as chemotherapy agents in the near future.

Topics: Animals; Antineoplastic Agents; Arachidonate 15-Lipoxygenase; Arachidonic Acid; Drug Design; Humans; Linoleic Acid; Lipoxygenase Inhibitors; Neoplasms; Patents as Topic; PPAR gamma

Milk fat is characterized by extensive pro-health activity. Its unique components, such as: short chain saturated fatty acids, conjugated linoleic acid (CLA), vaccenic acid, ether lipids (alkiloglicerols and alkiloglicerophospholipids), 13-methyltetradecanic acid and bioactive components of antioxidative activity, are important in prophylaxis, and even in therapy of cancer diseases. Advantageous influence to maintain pro- and antioxidative balance of organism is revealed by the components of milk fat: conjugated linoleic acid, vitamins A and E, and coenzyme Q10. Moreover, vitamin D3, phospholipids, ether lipids, cholesterol and 13-methyltetradecanic acid also reveal antioxidative activity.

Topics: Animals; Antioxidants; Cholecalciferol; Dietary Fats; Humans; Linoleic Acid; Milk; Neoplasms; Phospholipids; Ubiquinone; Vitamin A; Vitamin E

The pineal hormone melatonin is involved in the circadian regulation and facilitation of sleep, the inhibition of cancer development and growth, and the enhancement of immune function. Individuals, such as night shift workers, who are exposed to light at night on a regular basis experience biological rhythm (i.e., circadian) disruption including circadian phase shifts, nocturnal melatonin suppression, and sleep disturbances. Additionally, these individuals are not only immune suppressed, but they are also at an increased risk of developing a number of different types of cancer. There is a reciprocal interaction and regulation between sleep and the immune system quite independent of melatonin. Sleep disturbances can lead to immune suppression and a shift to the predominance in cancer-stimulatory cytokines. Some studies suggest that a shortened duration of nocturnal sleep is associated with a higher risk of breast cancer development. The relative individual contributions of sleep disturbance, circadian disruption due to light at night exposure, and related impairments of melatonin production and immune function to the initiation and promotion of cancer in high-risk individuals such as night shift workers are unknown. The mutual reinforcement of interacting circadian rhythms of melatonin production, the sleep/wake cycle and immune function may indicate a new role for undisturbed, high quality sleep, and perhaps even more importantly, uninterrupted darkness, as a previously unappreciated endogenous mechanism of cancer prevention.

Topics: Animals; Breast Neoplasms; Cell Transformation, Neoplastic; Circadian Rhythm; Dietary Fats; Female; Humans; Immune Tolerance; Linoleic Acid; Male; Melatonin; Mice; Neoplasms; Pineal Gland; Sleep; Sleep Disorders, Circadian Rhythm; Suprachiasmatic Nucleus; Young Adult

Omega-3 (n-3) and omega-6 (n-6) polyunsaturated fatty acids (PUFAs) are essential fatty acids necessary for human health. Currently, the Western diet contains a disproportionally high amount of n-6 PUFAs and low amount of n-3 PUFAs, and the resulting high n-6/n-3 ratio is thought to contribute to cardiovascular disease, inflammation, and cancer. Studies in human populations have linked high consumption of fish or fish oil to reduced risk of colon, prostate, and breast cancer, although other studies failed to find a significant association. Nonetheless, the available epidemiological evidence, combined with the demonstrated effects of n-3 PUFAs on cancer in animal and cell culture models, has motivated the development of clinical interventions using n-3 PUFAs in the prevention and treatment of cancer, as well as for nutritional support of cancer patients to reduce weight loss and modulate the immune system. In this review, we discuss the rationale for using long-chain n-3 PUFAs in cancer prevention and treatment and the challenges that such approaches pose in the design of clinical trials.

Topics: alpha-Linolenic Acid; Animals; Arachidonic Acid; Clinical Trials as Topic; Eicosapentaenoic Acid; Fatty Acids, Omega-3; Fatty Acids, Omega-6; Humans; Linoleic Acid; Lipid Peroxidation; Neoplasms; Nutritional Support

Substantial evidence supports a functional role for cyclooxygenase- and lipoxygenase-catalyzed arachidonic and linoleic acid metabolism in cancer development. Genetic intervention studies firmly established cause-effect relations for cyclooxygenase-2, but cyclooxygenase-1 may also be involved. In addition, pharmacologic cyclooxygenase inhibition was found to suppress carcinogenesis in both experimental mouse models and several cancers in humans. Arachidonic acid-derived eicosanoid or linoleic acid-derived hydro[peroxy]fatty acid signaling are likely to be involved impacting fundamental biologic phenomena as diverse as cell growth, cell survival, angiogenesis, cell invasion, metastatic potential and immunomodulation. However, long chain unsaturated fatty acid oxidation reactions indicate antipodal functions of distinct lipoxygenase isoforms in carcinogenesis, i.e., the 5- and platelet-type 12-lipoxygenase exhibit procarcinogenic activities, while 15-lipoxygenase-1 and 15-lipoxygenase-2 may suppress carcinogenesis.

Topics: Animals; Antineoplastic Agents; Apoptosis; Arachidonate Lipoxygenases; Arachidonic Acid; Cell Differentiation; Cell Proliferation; Cell Survival; Cell Transformation, Neoplastic; Cyclooxygenase 2; Cyclooxygenase Inhibitors; Eicosanoic Acids; Humans; Isoenzymes; Linoleic Acid; Lipid Peroxides; Lipoxygenase; Neoplasm Invasiveness; Neoplasms; Neovascularization, Pathologic; Prostaglandin-Endoperoxide Synthases; Signal Transduction

Chemoprevention represents a highly promising approach for the control of cancer. That nonsteroidal anti-inflammatory drugs (NSAIDs) prevent colon and other cancers has led to novel approaches to cancer prevention. The known inhibitory effect of NSAIDs on the eicosanoid pathway prompted mechanistic and drug development work focusing on cyclooxygenase (COX), culminating in clinical trials of cyclooxygenase 2 (COX-2) inhibitors for cancer prevention or treatment. However, two COX-2 inhibitors have been withdrawn due to side effects. Here we review several pathways of the eicosanoid cascade that are relevant to cancer; summarize the evidence regarding the role of COX-2 as a target for cancer prevention; and discuss several of the molecular targets that may mediate the chemopreventive effect of NSAIDs. The clinically modest results obtained to date with COX-2 specific inhibitors used in cancer prevention; the multiple COX-2-independent targets of both NSAIDs and COX-2 inhibitors; and the limitations of some COX-2 inhibitors indicate that exploiting these (non-COX-2) molecular targets will likely yield effective new approaches for cancer chemoprevention.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Arachidonic Acid; Chemoprevention; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; Humans; Linoleic Acid; Membrane Proteins; Neoplasms; Prostaglandin-Endoperoxide Synthases

Experimental evidence indicates that n-3 fatty acids, especially the long-chain polyunsaturated fatty acids, unlike n-6 fatty acids could prevent cancer development. This survey shows that fatty acids could act through several mechanisms including the production of reactive oxygen species, the modulation of gene expression and signal transduction pathways, or the eicosanoid biosynthesis. Human genetics has underlined several polymorphisms in genes identified as possible targets of fatty acids which suggests that the link between nutritional intake and cancer prevention, especially the eventual anti-carcinogenic effects of n-3 fatty acids, depends on the genetic background. Further studies are needed to evaluate the effects of fatty acids on angiogenesis which represents a marker of a poor prognosis in cancer. Finally, the use of genomic technologies combined with nutritional strategies could provide a more understanding of the effects of n-3 fatty acid intake on cancer prevention.

Topics: Adipose Tissue; Apoptosis; Cyclooxygenase 2; Dietary Fats; DNA Damage; Food; Gene Expression Regulation; Linoleic Acid; Lipid Peroxidation; Neoplasms; Neovascularization, Pathologic; Peroxisome Proliferators; Polymorphism, Genetic; Prostaglandin-Endoperoxide Synthases; Protein Kinases; Signal Transduction

Physiological and pharmacological blood concentrations of melatonin inhibit tumorigenesis in a variety of in vivo and in vitro experimental models of neoplasia. Evidence indicates that melatonin's anticancer effects are exerted via inhibition of cell proliferation and a stimulation of differentiation and apoptosis. A new mechanism by which physiological and pharmacological blood levels of melatonin inhibit cancer growth in vivois via a melatonin-induced suppression of tumor linoleic acid (LA) uptake and its metabolism to the important mitogenic signaling molecule 13-hydroxyoctadecadienoic acid (13-HODE). Melatonin suppresses cAMP formation and inhibits tumor uptake of LA and its metabolism to 13-HODE via a melatonin receptor-mediated mechanism in both tissue-isolated rat hepatoma 7288 CTC and human breast cancer xenografts. It has been postulated that in industrialized societies, light at night, by suppressing melatonin production, poses a new risk for the development of breast cancer and, perhaps, other cancers as well. In support of this hypothesis, light during darkness suppresses nocturnal melatonin production and stimulates the LA metabolism and growth of rat hepatoma and human breast cancer xenografts. Nocturnal dietary supplementation with melatonin, at levels contained in a melatonin-rich diet, inhibits rat hepatoma growth via the mechanisms described above. The nocturnal melatonin signal organizes tumor metabolism and growth within circadian time structure that can be further reinforced by appropriately timed melatonin supplementation. Dietary melatonin supplementation working in concert with the endogenous melatonin signal has the potential to be a new preventive/therapeutic strategy to optimize the host/cancer balance in favor of host survival and quality of life.

Topics: Animals; Anticarcinogenic Agents; Antineoplastic Agents; Circadian Rhythm; Dietary Supplements; Disease Models, Animal; Humans; Light; Linoleic Acid; Melatonin; Neoplasms; Sleep

The cholesterol hypothesis implies that reducing the intake of saturated fatty acids and cholesterol and increasing that of polyunsaturated fatty acid are effective in lowering serum total cholesterol (TC), and thereby reducing the incidence of coronary heart disease (CHD). However, these dietary recommendations are essentially ineffective in reducing TC in the long run, but rather increase mortality rates from CHD and all causes. The reported "apparent relative risk of high TC in CHD mortality" (the ratio of mortality at the highest/lowest TC levels) varied several-fold among populations studied. The incidence of familial hypercholesterolemia (FH) in a population was proposed to be a critical factor in the observed variability, which could be accounted for by assuming that 1) the high CHD mortality rate in high-TC groups is mainly a reflection of the incidence and severity of FH, and 2) high TC is not a causative factor of CHD in non-FH cases. This interpretation is supported by recent observations that high TC is not positively associated with high CHD mortality rates among general populations more than 40-50 years of age. More importantly, higher TC values are associated with lower cancer and all-cause mortality rates among these populations, in which relative proportions of FH are likely to be low (circa 0.2%). Although the effectiveness of statins in preventing CHD has been accepted in Western countries, little benefit seems to result from efforts to limit dietary cholesterol intake or to TC values to less than approximately 260 mg/dl among the general population and the elderly. Instead, an unbalanced intake of omega6 over omega3 polyunsaturated fats favors the production of eicosanoids, the actions of which lead to the production of inflammatory and thrombotic lipid mediators and altered cellular signaling and gene expression, which are major risk factors for CHD, cancers, and shorter longevity. Based on the data reviewed here, it is urgent to change the direction of current cholesterol-related medication for the prevention of CHD, cancer, and all-cause mortality.

Topics: alpha-Linolenic Acid; Anticholesteremic Agents; Atherosclerosis; Coronary Disease; Docosahexaenoic Acids; Eicosapentaenoic Acid; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipoproteinemia Type II; Inflammation; Inflammation Mediators; Linoleic Acid; Neoplasms; Risk Factors; Thrombosis

Topics: Animals; Breast Neoplasms; Endothelin-1; Humans; Linoleic Acid; Melatonin; Neoplasms; Telomerase

Conjugated Linoleic Acids (CLA) are of great interest for analysts since techniques have been developed to determine the dietary occurrence of CLA with a good accuracy. CLA is found in animal products from ruminant sources as the result of biohydrogenation of polyunsaturated fatty acids in the rumen and as the consequence of the delta-9 desaturation of vaccenic acid in animal tissues. CLA can also be obtained in the laboratory by isomerisation of linoleic acid or by total chemical synthesis. While the "natural" isomer is rumenic acid (9c,11t-18:2), synthetic mixtures contain mainly two isomers: the 9c,11t- and the 10t,12c-18:2. Although CLA have been shown to be metabolized into desaturated and chain elongated products, it remains unclear whether these so-formed conjugated metabolites may be involved in the effects of CLA on fatty acid metabolism. Experiments carried out on animal models with CLA have shown different health benefits: anticarcinogenic, antiatherosclerotic effects, modulation of body composition , the "natural" CLA (9c,11t-18:2) being closely related to the protection against cancer and the 10t,12c-18:2 to the reduction of the fat mass. Nevertheless, recent findings have suggested adverse effects in mice. Most of the studies carried out on humans concern the influence of CLA on body composition and its possible inverse association with cancer. Since the results are still controversial and since very few data dealing with the safety of using CLA in long term feeding studies have so far been published, further works are warranted to consider the benefits of CLA for humans.

Topics: Animals; Arteriosclerosis; Body Composition; Disease Models, Animal; Humans; Linoleic Acid; Linoleic Acids, Conjugated; Neoplasms; Oleic Acids; Trans Fatty Acids

Topics: alpha-Linolenic Acid; Cholesterol; Clinical Trials as Topic; Coronary Disease; Humans; Japan; Linoleic Acid; Lipids; Neoplasms; Nutrition Policy; Nutritional Physiological Phenomena; Societies, Medical; Stroke

Conjugated linoleic acid (CLA) is a group of polyunsaturated fatty acids found in beef, lamb, and dairy products that exist as positional and stereo-isomers of octadecadienoate (18:2). Over the past two decades numerous health benefits have been attributed to CLA in experimental animal models including actions to reduce carcinogenesis, atherosclerosis, onset of diabetes, and body fat mass. The accumulation of CLA isomers and several elongated/desaturated and beta-oxidation metabolites have been found in tissues of animals fed diets with CLA. Molecular mechanisms of action appear to include modulation of eicosanoid formation as well as regulation of the expression of genes coding for enzymes known to modulate macronutrient metabolism. This review focuses on health benefits, metabolism, and potential mechanisms of action of CLA and postulates the implications regarding dietary CLA for human health.

Topics: Adipose Tissue; Animals; Arteriosclerosis; Dairy Products; Diabetes Mellitus; Diet; Dietary Fats, Unsaturated; Disease Models, Animal; Humans; Linoleic Acid; Meat; Mice; Neoplasms; Rats; Stereoisomerism

Cell proliferation, cell injury and aging are connected with changes in the cell membrane structure. Apparently these changes activate, in mammalian as well as in plant cells, lipases which liberate polyunsaturated fatty acids (PUFAs). PUFAs are the substrates for lipoxygenases which convert them to corresponding hydroperoxides (LOOHs). Lipoxygenases commit suicide by releasing iron ions. LOOHs react with iron ions to generate radicals. Thus, a nonenzymic lipid peroxidation process (LPO) is induced. It is speculated that the change from enzymic to nonenzymic LPO is connected with the switch from apoptosis to necrosis and that LOOHs produced in enzymic reactions are degraded specifically to signal compounds which induce physiological responses, while nonenzymic reactions seem to induce generation of reactive oxygen species, cell death and age related diseases. Enzymic and nonenzymic LPO processes concern all PUFAs not only arachidonic acid. The main PUFA in mammals is linoleic acid. Since these products serve signalling functions, different degradation paths of linoleic-hydroperoxides are described in detail and the physiological properties of LPO products are discussed in relation to aging and age related diseases.

Topics: Aging; Animals; Apoptosis; Disease; Energy Intake; Humans; Linoleic Acid; Lipid Peroxidation; Neoplasms

Convincing evidence from rodent models of carcinogenesis indicates that cis-9,trans-11 (c9t11) conjugated linoleic acid (CLA) is a potent naturally occurring anti-carcinogen in the human diet. CLA has been reported to alter the fatty acid composition of biological tissues in a manner that increases their oxidative stability. However, recent information suggests that an antioxidant role for CLA does not seem plausible. Given the knowledge that c9t11 CLA is present in a wide range of meat and dairy food products, our studies have begun to investigate mechanisms by which CLA-enriched milk fat exerts its anti-carcinogenic effects. An oxidative mechanism appears to be involved in its growth-suppressive effects, since supplementation of growth culture medium with CLA (17-71.5 microM) made breast cancer cells more susceptible to lipid peroxidation. Studies have indicated that cancer cells may become enriched in CLA during growth in culture. This may make intracellular lipids more susceptible to ordinary levels of oxidative stress, to the point of producing a cytotoxic effect.

Topics: Animals; Arachidonic Acid; Humans; Linoleic Acid; Neoplasms; Oxidants; Phospholipids

Many nutritional, hormonal, and environmental factors affect carcinogenesis and growth of established tumors in rodents. In some cases, these factors may either enhance or attenuate the neoplastic process. Recent experiments performed in our laboratory using tissue-isolated rat hepatoma 7288CTC in vivo or during perfusion in situ have demonstrated new interactions among four of these factors. Two agents, dietary linoleic acid (C18:2n6) and "light at night," enhanced tumor growth, and two others, melatonin and n3 fatty acids, attenuated growth. Linoleic acid stimulated tumor growth because it is converted by hepatoma 7288CTC to the mitogen, 13-hydroxyoctadecadienoic acid (13-HODE). Melatonin, the neurohormone synthesized and secreted at night by the pineal gland, and dietary n3 fatty acids are potent antitumor agents. Both inhibited tumor linoleic acid uptake and 13-HODE formation. Artificial light, specifically "light at night," increased tumor growth because it suppressed melatonin synthesis and enhanced 13-HODE formation. Melatonin and n3 fatty acids acted via similar or identical G(i) protein-coupled signal transduction pathways, except that melatonin receptors and putative n3 fatty acid receptors were used. The results link the four factors in a common mechanism and provide new insights into the roles of dietary n6 and n3 polyunsaturated fatty acid intake, "light at night," and melatonin in cancer prevention in humans.

Topics: Animals; Antioxidants; Fatty Acids, Unsaturated; Humans; Linoleic Acid; Melatonin; Neoplasms

Conjugated linoleic acid (CLA) refers to a group of positional and geometric isomers of the omega-6 essential fatty acid linoleic acid (cis-9, cis-12, octadecadienoic acid). In humans evidence is currently ambiguous as to whether CLA supplementation has a significant effect on body composition. Despite favorable changes in lipid levels in animal models, a beneficial effect in humans has not yet been established. While some of the changes reported are consistent with an improved lipid profile, declines in HDL and increases in lipoprotein (a) have also been observed in some subjects. Available evidence suggests CLA supplementation has no impact on immune system performance in healthy subjects.

Topics: Animals; Body Composition; Cardiovascular Diseases; Dietary Supplements; Dose-Response Relationship, Drug; Humans; Insulin Resistance; Linoleic Acid; Neoplasms

N-6 fatty acids are essential for normal growth, development and health, and so extreme care is necessary before deciding that they are harmful. Theoretical and epidemiological evidence suggests the involvement of n-6 polyunsaturated fatty acids (PUFAs) in disease progression or prevention; however, n-6 function cannot be considered in isolation but needs to be seen as part of the complex of nutrient interactions with n-3 fatty acids (which compete for the same enzymatic pathways) and antioxidants. Insulin sensitivity might be the common factor relating disease to fatty acid metabolism both within and between the fatty acid pathways. High linoleate to arachidonate concentrations have been observed in insulin resistance, diabetic complications and some tumours, but these are multifactorial processes that include many lifestyle determinants and it is therefore wrong to condemn only n-6 fatty acids in their etiology. The results based on the criteria for assessing diet and disease are still insufficient to declare n-6 fatty acids a serious health risk; at most, the verdict should be "not proven". The question may never be conclusively answered not only because prospective dietary intervention trials (unlike those with n-3 fish oil capsules) are fraught with dosage and compliance problems, but also because of high background linoleate consumption. Tissue fatty acid composition may be a suitable biomarker for PUFA intake but there are many theoretical and methodological problems concerning other suitable markers because of the multiplicity of their biological effects. Before making evidence-based dietary recommendations, future research should consider: 1) how n-3 and n-6 dietary PUFAs affect the physiological balance (dose-response) of their derivatives such as eicosanoids and the newly-discovered fatty acid amides; 2) the metabolic interactions between n-6 and n-3 fatty acid pathways (including gene-nutrient effects); 3) the need for antioxidant cover (quantity and quality); 4) prospective intervention trials.

Topics: Animals; Arteriosclerosis; Cardiovascular Diseases; Fatty Acids, Omega-6; Fatty Acids, Unsaturated; Humans; Insulin Resistance; Linoleic Acid; Neoplasms

Conjugated linoleic acid (CLA), a derivative of a fatty acid linoleic acid (LA), has been reported to decrease tumorigenesis in animals. CLA is unique because unlike most antioxidants which are components of plant products, it is present in food from animal sources such as dairy foods and meats. CLA concentrations in dairy products typically range from 2.9 to 8.92 mg/g fat of which the 9-cis, 11-trans isomer makes up to 73% to 93% of the total CLA. Low concentrations of CLA are found in human blood and tissues. In vitro results suggest that CLA is cytotoxic to MCF-7 cells and it inhibits the proliferation of human malignant melanoma and colorectal cancer cells. In animal studies, CLA has inhibited the development of mouse epidermal tumors, mouse forestomach cancer and rat mammary cancer. Hamsters fed CLA collectively had significantly reduced levels of plasma total cholesterol, non-high-density lipoprotein cholesterol, (combined very-low and low-density lipoprotein) and triglycerides with no effect on high-density lipoprotein cholesterol, as compared to controls. Dietary CLA modulated certain aspects of the immune defense but had no obvious effect on the growth of an established, aggressive mammary tumor in mice. It is now thought that CLA itself may not have anti-oxidant capabilities but may produce substances which protect cells from the detrimental effects of peroxides. There is, however, insufficient evidence from human epidemiological data, and very few of the animal studies have shown a dose-response relationship with the quantity of CLA feed and the extent of tumor growth. Further research with tumor models is needed to test the efficacy and utility of CLA in cancer and other disease prevention and form the basis of evaluating its effect in humans by observational studies and clinical trials.

Topics: Animals; Antioxidants; Arteriosclerosis; Dairy Products; Humans; Immunity; Linoleic Acid; Meat; Neoplasms

Improved means of cancer prevention and treatment remain key goals of global health programmes. This is particularly true in Western society, where the elderly represent a large proportion of the population, and where the likelihood of tumour development is compounded by risk factors such as poor fibre/high fat diets and environmental pollution. Dietary intervention represents an attractive, non-invasive means of providing anticancer preventative and therapeutic benefits to at-risk individuals. This review focuses on the evidence for anticancer properties of bovine milk and milk-derived components. Evidence of a role for whole milk constituents, as well as purified minor components, in combating tumorigenesis is outlined. Shortcomings in current studies are highlighted, and future opportunities for targeted research to characterize important anticancer properties of milk are discussed.

Topics: Animals; Antioxidants; Biological Products; Calcium; Diet, Fat-Restricted; Dietary Fats, Unsaturated; Humans; Linoleic Acid; Milk; Milk Proteins; Minerals; Models, Animal; Neoplasms; Phospholipids; Rats

Topics: Animal Feed; Animals; Chromatography, Gas; Chromatography, High Pressure Liquid; Diabetes Mellitus, Type 1; Humans; Isomerism; Linoleic Acid; Meat; Neoplasms; Safety

New results on the physiological properties of conjugated linoleic acid have been published by several working groups, especially showing the effects of single conjugated linoleic acid isomers on carcinogenesis and body composition. Recently, other studies have shown that conjugated linoleic acid has an influence on diabetes mellitus, platelet aggregation and the immune system. Conjugated linoleic acid was found to modify prostaglandin metabolism and delta9-desaturase activity and influence apoptosis. Furthermore, improved analytical methods using 13C nuclear magnetic resonance and silver ion high performance liquid chromatography are available to investigate the composition of conjugated linoleic acid mixtures and the exact structure of separated isomers. Also, the synthesis of isolated isomers is described, as published by different authors, in order to determine further the effects of each single conjugated linoleic acid isomer. In addition, new data on the contents of conjugated linoleic acid in foods, human adipose tissue and fluids are given in this review. More data need to be obtained using isolated isomers, with particular emphasis on studies in humans.

Topics: Adipose Tissue; Animals; Arteriosclerosis; Body Composition; Food Analysis; Humans; Linoleic Acid; Neoplasms

Replacement of saturated fat by the major dietary polyunsaturated fat linoleic acid reduces blood cholesterol concentrations and the risk of coronary artery disease. However, there is concern that long-term consumption of large amounts of linoleic acid might increase cancer risk. We reviewed the epidemiologic and experimental literature on linoleic acid intake and cancer risk and performed additional meta-analyses of risk estimates from case-control and prospective cohort studies. None of the combined estimates from within-population studies indicated a significantly increased risk of cancer with high compared with low intakes of linoleic acid or polyunsaturated fat. For case-control studies, the combined relative risks were 0.84 (95% CI: 0.71, 1.00) for breast, 0.92 (95% CI: 0.85, 1.08) for colorectal, and 1.27 (95% CI: 0.97, 1.66) for prostate cancer. For prospective cohort studies, combined relative risks were 1.05 (95% CI: 0.83, 1.34) for breast, 0.92 (95% CI: 0.70, 1.22) for colon, and 0.83 (95% CI: 0.56, 1.24) for prostate cancer. Ecologic comparisons of populations showed positive associations between cancer rates and per capita use of animal or saturated fat, but less so with per capita use of vegetable oil or polyunsaturated fat. Controlled studies of coronary artery disease in men did not, except for 1 study, show an increased cancer incidence after consumption of diets with a very high linoleic acid content for several years. Animal experiments indicated that a minimum amount of linoleic acid is required to promote growth of artificially induced tumors in rodents; but above this threshold, linoleic acid did not appear to have a specific tumor-promoting effect. Although current evidence cannot exclude a small increase in risk, it seems unlikely that a high intake of linoleic acid substantially raises the risks of breast, colorectal, or prostate cancer in humans.

Topics: Animals; Breast Neoplasms; Case-Control Studies; Cohort Studies; Colorectal Neoplasms; Female; Humans; Linoleic Acid; Male; Neoplasms; Prospective Studies; Prostatic Neoplasms; Risk Factors

Oxidative reactions have been implicated in the development of numerous diseases including atherosclerosis and cancer. Oxidation of lipids, proteins, and nucleic acids can result in loss of membrane integrity and function, inactivation of enzymes, modification of lipoproteins, and chemical alteration of DNA. Active oxygen species, transition metals, reducing agents, and enzymes such as lipoxygenase are all involved in the catalysis of oxidative reactions. Since lipid oxidation catalysts and active oxygen species are ubiquitous to all biological systems and since lipid oxidation products can enter the body via oxidized foods, numerous endogenous antioxidant systems have been developed. Endogenous antioxidant systems include antioxidant enzymes, free radical scavengers, and metal chelators. The purpose of this review is to examine the potential of nonessential dietary components that inhibit oxidative reactions in foods and biological tissues.

Topics: Animals; Antioxidants; Arteriosclerosis; Carnosine; Diet; Humans; Linoleic Acid; Linoleic Acids; Neoplasms; Phenols; PQQ Cofactor; Quinolones

This presentation focuses on research that could theoretically be applied to implement the strategy of general population chemoprevention. The concept is based on the premise of enhancing foods with known anticarcinogens through either agricultural methods or food-processing technologies. Two areas of our work are described: (a) garlic cultivated with selenium fertilization and (b) foods high in conjugated linoleic acid. Both selenium and conjugated linoleic acid are powerful chemopreventive agents in the animal tumor model. The rationale of delivering these two specific compounds through the food system will be developed. Preliminary studies will be summarized to show the feasibility of this approach in suppressing carcinogen-induced mammary cancer in rats. Finally, the advantages of using foods to provide anticarcinogens to the general population as part of a chemopreventive strategy will also be discussed.

Topics: Animals; Anticarcinogenic Agents; Diet; Dietary Fats; Food; Garlic; Humans; Linoleic Acid; Linoleic Acids; Neoplasms; Plants, Medicinal; Selenium

During a study of the mechanism of cancer cachexia, a debilitating condition in which catabolism of host muscle and adipose tissue occurs, it has been observed that the process can be effectively reversed in vivo by the polyunsaturated fatty acid, eicosapentaenoic acid (EPA), but not by other PUFA of either the n-3 or n-6 series. In vitro studies showed that EPA blocked the action of a tumour-produced catabolic factor at the level of the adipocyte, and that the effect of EPA also extended to beta-adrenergic stimuli and polypeptide hormones. Again the effect was specific to EPA and appeared to arise from an inhibition of the elevation of cyclic AMP levels in adipocytes in response to varied stimuli. Using isoprenaline stimulated lipolysis as a model system we have shown that EPA has a direct inhibitory effect on isoprenaline-stimulated adenylate cyclase in isolated plasma membrane fractions with half maximal inhibition at a concentration of 165 microM. The inhibitory effect was specific for EPA and was not shown by docosahexaenoic or arachidonic acids. The inhibitory effect of EPA on adenylate cyclase showed properties similar to hormonal inhibition of the enzyme in that it was (i) GTP-dependent, (ii) non-competitive with isoprenaline, (iii) eliminated following treatment of either adipocytes or plasma membrane fractions with pertussis toxin, which is known to ADP-ribosylate the alpha-subunit of an inhibitory guanine nucleotide-regulatory protein (Gi), thus leading to its inactivation. This suggests that inhibition of cyclic AMP formation by EPA was due, at least in part, to a Gi-mediated inhibition of adenylate cyclase activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adenocarcinoma; Adenylyl Cyclases; Adipose Tissue; Animals; Cachexia; Colonic Neoplasms; Cyclic AMP; Dietary Fats; Eicosapentaenoic Acid; Enzyme Activation; Fatty Acids, Omega-3; Fatty Acids, Unsaturated; Gene Expression Regulation; Genes, ras; GTP-Binding Proteins; Humans; Isoproterenol; Linoleic Acid; Linoleic Acids; Lipid Metabolism; Lipolysis; Mice; Neoplasms; Signal Transduction

Topics: Animals; Autoimmune Diseases; B-Lymphocytes; Dietary Fats; Evaluation Studies as Topic; Fatty Acids, Unsaturated; Guinea Pigs; Humans; Immunocompetence; Infections; Linoleic Acid; Linoleic Acids; Lymphocyte Activation; Mice; Neoplasms; Rats; T-Lymphocytes

Topics: Animals; Chromosome Aberrations; Cricetinae; Cricetulus; Dietary Fats; Fatty Acids; Fatty Acids, Omega-3; Global Health; Humans; Linoleic Acid; Linoleic Acids; Mice; Mutagenicity Tests; Mutation; Neoplasms; Neoplasms, Experimental; Prostaglandins; Rats

Recently, lactate has been considered as an alternative direct energy substance to glucose for tumor proliferation and metastasis. Meanwhile, mitochondria, as important energy-supplying organelles, are also closely related to tumor progression. Consequently, a new research direction for lactate comprises lactate deprivation coupled with mitochondria-targeted phototherapy to achieve a safer and more effective strategy against tumor metastasis. Herein, linoleic acid-conjugated hyaluronic acid (HL), disulfide bond-rich nanovehicle (mesoporous silica, MOS), mitochondria-targeted IR780 (M780) and lactate oxidase (LOD) are rationally designed as a specific-targeting metabolism nanomodulator (HL/MOS@M780&LOD NPs), fulfilling the task of simultaneous depriving cells of lactate and damaging mitochondria to prevent tumor metastasis. Interestingly, M780-mediated photodynamic therapy (PDT) and LOD-mediated starvation therapy can effectively exacerbate the hypoxia state of tumor cells, thereby increasing the free iron levels to activate ferroptosis. On one hand, pyruvic acid and H

Topics: Cell Line, Tumor; Humans; Hydrogen Peroxide; Hypoxia; Iron; Lactates; Linoleic Acid; Nanoparticles; Neoplasms; Photochemotherapy; Tumor Microenvironment

Melatonin, the circadian nighttime neurohormone, and eicosapentaenoic acid (EPA) and docosahexaenoic acids (DHA), which are omega-3 fatty acids (FA) found in high concentrations in fish oil (FO) and plants, abrogate the oncogenic effects of linoleic acid (LA), an omega-6 FA, on the growth of rodent tumors and human breast, prostate, and head and neck squamous cell carcinoma (HNSCC) xenografts in vivo. Here we determined and compared the long-term effects of these inhibitory agents on tumor regression and LA uptake and metabolism to the mitogenic agent 13-[S]-hydroxyoctadecadienoic acid (13-[S]-HODE) in human prostate cancer 3 (PC3) and FaDu HNSCC xenografts in tumor-bearing male nude rats. Rats in this study were split into 3 groups and fed one of 2 diets: one diet containing 5% corn oil (CO, high LA), 5% CO oil and melatonin (2 μg/mL) or an alternative diet 5% FO (low LA). Rats whose diet contained melatonin had a faster rate of regression of PC3 prostate cancer xenografts than those receiving the FO diet, while both in the melatonin and FO groups induced the same rate of regression of HNSCC xenografts. The results also demonstrated that dietary intake of melatonin or FO significantly inhibited tumor LA uptake, cAMP content, 13-[S]-HODE formation, [³H]-thymidine incorporation into tumor DNA, and tumor DNA content. Therefore, long-term ingestion of either melatonin or FO can induce regression of PC3 prostate and HNSCC xenografts via a mechanism involving the suppression of LA uptake and metabolism by the tumor cells.

Topics: Animals; Diet; Heterografts; Humans; Linoleic Acid; Linoleic Acids; Male; Melatonin; Neoplasms; Rats; Rats, Nude

Effective and targeted delivery of siRNA to tumor cells is a prerequisite to achieving their therapeutic effects. Survivin is up-regulated in tumor cells and is associated with resistance to therapy. Therefore, siRNA-mediated silencing of survivin is a potential therapeutic strategy for cancer. The aim of the study was to examine whether polymeric hybrid micelles can be used to effectively deliver siRNAs into cells.. First, linoleic acid (LA) was conjugated to polyethylenimine (PEI) and methoxy-polyethyleneglycol (mPEG) and two amphiphilic polymers (PEI-LA and mPEG-LA) were obtained. Polymeric hybrid micelle (PHM) was then prepared and characterized by self-assembly of PEI-LA and mPEG-LA at different percentages of the two amphiphilic polymers. A PHM/siRNA complex with optimized composition and good biocompatibility was then prepared and its cellular uptake, biodistribution, and antitumor effects were investigated.. Survivin siRNA was efficiently delivered to the cells. It reduced survivin protein expression and greatly suppressed tumor growth. Moreover, siRNA loaded in PHM gathered in a solid tumor in mice and achieved an improved anticancer effect compared to naked siRNA.. PHM is a promising and safe vehicle for siRNA delivery and may find utility in cancer therapy.

Topics: A549 Cells; Animals; Cell Survival; Female; Humans; Linoleic Acid; Mice, Inbred BALB C; Mice, Nude; Micelles; Neoplasms; Polyethylene Glycols; Polyethyleneimine; RNA, Small Interfering; Survivin; Tumor Burden

The cardioprotective properties of linoleic acid (LA), a major n-6 (ω-6) polyunsaturated fatty acid (PUFA), have been recognized, but less is known about its associations with other causes of death. Relatively little is also known about how the minor n-6 PUFAs-γ-linolenic acid (GLA), dihomo-γ-linolenic acid (DGLA), and arachidonic acid (AA)-relate to mortality risk.. We investigated the associations of serum n-6 PUFAs, an objective biomarker of exposure, with risk of death in middle-aged and older men and whether disease history modifies the associations.. We included 2480 men from the prospective Kuopio Ischaemic Heart Disease Risk Factor Study, aged 42-60 y at baseline in 1984-1989. The stratified analyses by baseline disease status included 1019 men with a history of cardiovascular disease (CVD), cancer, or diabetes and 1461 men without a history of disease.. During the mean follow-up of 22.4 y, 1143 deaths due to disease occurred. Of these, 575 were CVD deaths, 317 were cancer deaths, and 251 were other-cause deaths. A higher serum LA concentration was associated with a lower risk of death from any cause (multivariable-adjusted HR for the highest compared with the lowest quintile: 0.57; 95% CI: 0.46, 0.71; P-trend < 0.001) and with deaths due to CVD (extreme-quintile HR: 0.54; 95% CI: 0.40, 0.74; P-trend < 0.001) and non-CVD or noncancer causes (HR: 0.48; 95% CI: 0.30, 0.76; P-trend = 0.001). Serum AA had similar, although weaker, inverse associations. Serum GLA and DGLA were not associated with risk of death, and none of the fatty acids were associated with cancer mortality. The results were generally similar among those with or without a history of major chronic disease (P-interaction > 0.13).. Our findings showed an inverse association of a higher biomarker of LA intake with total and CVD mortality and little concern for risk, thus supporting the current dietary recommendations to increase LA intake for CVD prevention. The finding of an inverse association of serum AA with the risk of death needs replication in other populations.

Topics: 8,11,14-Eicosatrienoic Acid; Adult; Arachidonic Acid; Biomarkers; Body Mass Index; Cardiovascular Diseases; Diabetes Mellitus; Diet; Fatty Acids, Omega-6; Follow-Up Studies; gamma-Linolenic Acid; Humans; Incidence; Linoleic Acid; Male; Middle Aged; Mortality; Neoplasms; Prospective Studies; Risk Factors; Socioeconomic Factors

In this letter to editor, I hypothesize a potential affinity of retinol saturase (RetSat) enzyme towards a conjugated trienoic fatty acid; alpha-eleostearic acid (α-ESA) and subsequent hindrance of the action on its usual substrate; all trans retinol. Hence, RetSat is speculated to be involved in a rapid unusual conversion of α-ESA to conjugated linoleic acid (CLA), giving a less priority to its usual substrate all trans retinol, which would subsequently be converted into "all trans retinoic acid" (atRA). Otherwise, all trans retinol is converted by RetSat into all-trans-13,14-dihydroretinol and eventually forms all-trans-13,14-dihydroretinoic acid, but not the atRA. The atRA controls differentiation, proliferation and apoptosis of cells and it's deficiencies end up as neoplasms. Thus, here it is emphasized that safeguarding atRA would help controlling cell division and growth in a favourable manner. Hence, inhibition of RetSat could be a hot target to control unwarranted cell growths within the body. This hypothesis could be easily tested in a RetSat ablated (RetSat -/-) animal model or using antagonists on RetSat activity or α-ESA.

Topics: Animals; Cell Differentiation; Cell Division; Humans; Linoleic Acid; Linoleic Acids, Conjugated; Linolenic Acids; Lipid Metabolism; Metabolomics; Neoplasms; Tretinoin; Vitamin A

One of the goals for the development of more effective cancer therapies with reduced toxic side effects is the optimization of innovative treatments to selectively kill tumor cells. The use of nanovectors loaded with targeted therapeutic payloads is one of the most investigated strategies. In this paper superparamagnetic iron oxide nanoparticles (SPIONs) coated by a silica shell or uncoated, were functionalized with single-layer and bi-layer conjugated linoleic acid (CLA). Silica was used to protect the magnetic core from oxidation, improve the stability of SPIONs and tailor their surface reactivity. CLA was used as novel grafting biomolecule for its anti-tumor activity and to improve particle dispersibility. Mouse breast cancer 4T1 cells were treated with these different SPIONs. SPIONs functionalized with the highest quantity of CLA and coated with silica shell were the most dispersed. Cell viability was reduced by SPIONs functionalized with CLA in comparison with cells which were untreated or treated with SPIONs without CLA. As regards the types of SPIONs functionalized with CLA, the lowest viability was observed in cells treated with uncoated SPIONs with the highest quantity of CLA. In conclusion, the silica shell free SPIONs functionalized with the highest amount of CLA can be suggested as therapeutic carriers because they have the best dispersion and ability to decrease 4T1 cell viability.

Topics: Animals; Cell Survival; Humans; Iron; Linoleic Acid; Magnetite Nanoparticles; Mice; Neoplasms; Silicon Dioxide

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Arachidonic Acid; Carcinogenesis; Carcinogens; Dinoprostone; Humans; Linoleic Acid; Linoleic Acids; Linoleic Acids, Conjugated; Neoplasms; Rats

Currently, the phosphatidylethanolamine-based, pH-sensitive, liposome drug-delivery system has been widely developed for efficient, targeted cancer therapy. However, the mechanism of pH sensitivity was unclear; it is a main obstacle in controlling the preparation of pH-sensitive liposomes (PSLs).Therefore, our research is aimed at clarifying the pH-response mechanism of the various molecules that compose liposomes. We chose the small pH-sensitive molecules oleic acid (OA), linoleic acid (LA) and cholesteryl hemisuccinate (CHEMS) and the fundamental lipids cholesterol and phosphatidylethanolamine (PE) as test molecules. The PSLs were prepared using the thin-film hydration method and characterized in detail at various pH values (pH 5.0, 6.0 and 7.4), including particle size, ζ-potential, drug encapsulation efficiency and drug loading. The surface structure was observed by transmission electron microscopy (TEM), and the electrical conductivity of the liposome dispersion was also tested. The calorimetric analysis was conducted by Nano-differential scanning calorimetry (Nano-DSC). The in vitro drug release profile showed that PSLs exhibit good pH sensitivity. At neutral pH, the particle size was approximately 150nm, and it dramatically increased at pH 5.0. The ζ-potential increased as the pH decreased. The Nano-DSC results showed that cholesterol and CHEMS can both increase the stability and phase transfer temperature of PSLs. Conductivity increased to a maximum at pH 5.0 and was rather low at pH 7.4. In conclusion, results show that the three kinds of liposomes have pH responsive release characteristics in acidic pH. The OA-PSLs have a pH sensitive point of 5. Since CHEMS has a cholesterol-like structure, it can stabilizes the phospholipid bilayer under neutral conditions as shown in the Nano-DSC data, and because it has a special steroidal rigid structure, it exhibits better pH response characteristics under acidic conditions.

Topics: Calorimetry, Differential Scanning; Cholesterol Esters; Drug Delivery Systems; Electric Conductivity; Hot Temperature; Humans; Hydrogen-Ion Concentration; Linoleic Acid; Liposomes; Microscopy, Electron, Transmission; Nanotechnology; Neoplasms; Oleic Acid; Phosphatidylethanolamines; Surface Properties; Temperature; Tumor Microenvironment

Hypoxia-inducible transcription factors (HIF) form heterodimeric complexes that mediate cell responses to hypoxia. The oxygen-dependent stability and activity of the HIF-α subunits is traditionally associated to post-translational modifications such as hydroxylation, acetylation, ubiquitination, and phosphorylation. Here we report novel evidence showing that unsaturated fatty acids are naturally occurring, non-covalent structural ligands of HIF-3α, thus providing the initial framework for exploring its exceptional role as a lipid sensor under hypoxia.

Topics: Apoptosis Regulatory Proteins; Basic Helix-Loop-Helix Transcription Factors; Cloning, Molecular; Crystallography, X-Ray; Escherichia coli; Gene Expression; Humans; Ligands; Linoleic Acid; Models, Molecular; Monoglycerides; Neoplasms; Oleic Acid; Protein Binding; Protein Structure, Secondary; Protein Structure, Tertiary; Recombinant Proteins; Repressor Proteins; Signal Transduction; Stearic Acids; Tissue Array Analysis

Src homology-2 domain-containing protein tyrosine phosphatase (Shp2), a novel proto-oncogenic protein, is an important target in cancer therapy research. Approximately 2000 plant extracts were screened to find its natural specific inhibitors, with the ethyl acetate (EtOAc) active extract of the root of Angelica dahurica showing considerable inhibitory effects (IC(50)=21.6 mg/L). Bioguided isolation of EtOAc extract led to 13 compounds, including 10 fatty acids and derivatives. All these compounds were isolated from the plant for the first time. The inhibitory effects of these compounds on the enzyme activities of Shp2, VH1-related human protein (VHR), and hematopoietic protein tyrosine phosphatase (HePTP) were investigated. 8Z,11Z-Feptadecadienoic acid (4), 14Z,17Z-tricosadienoic acid (5), caffeic acid (9), and 2-hydroxy-3-[(1-oxododecyl) oxy]propyl-β-d-glucopyranoside (11) showed considerable selective inhibition of Shp2 activity. After treatment of HepG2 cells with the compounds, only compound 5, a polyunsaturated fatty acid, strongly induced poly (ADP-ribose) polymerase (PARP) cleavage in a dose- and time-dependent manner and increased the activities of caspase-3, caspase-8, and caspase-9 at 100 μM. Compound 5 also inhibited colony formation of HepG2 cells in a dose-dependent manner. Thus, this study reported fatty acids as specific Shp2 inhibitors and provided the molecular basis of one active compound as novel potential anticancer drug.

Topics: Angelica; Antineoplastic Agents, Phytogenic; Apoptosis; Enzyme Inhibitors; Fatty Acids; Hep G2 Cells; Humans; Neoplasms; Plant Extracts; Plant Roots; Protein Tyrosine Phosphatase, Non-Receptor Type 11

Reactive oxygen species, along with reactive nitrogen species, may play an important role in the pathogenesis and progress of many diseases, including cancer, diabetes and sickle cell disease. It has been postulated that hydroxyurea, one of the main treatments in sickle cell disease, achieves its activity partly also through its antioxidant properties. A series of hydroxyurea derivatives of L- and D-amino acid amides and cycloalkyl-N-aryl-hydroxamic acids was synthesized and investigated for their radical scavenging activity, chelating properties and antioxidant activity. All the compounds showed exceptional antiradical activities. For example, free radical scavenging activities of investigated hydroxyureas were higher than the activity of standard antioxidant, butylated hydroxyanisole (BHA). Moreover, most of the investigated hydroxamic acids were stronger Fe²⁺ ion chelators than quercetin. In addition, the investigated compounds, especially hydroxamic acids, were proven to be excellent antioxidants. They were as effective as BHA in inhibiting β-carotene-linoleic acid coupled oxidation. It is reasonable to assume that the antioxidant activity of the investigated compounds could contribute to their previously proven biological properties as cytostatic and antiviral agents.

Topics: Anemia, Sickle Cell; beta Carotene; Biphenyl Compounds; Butylated Hydroxyanisole; Butylated Hydroxytoluene; Free Radical Scavengers; Humans; Hydroxamic Acids; Hydroxyurea; Iron; Iron Chelating Agents; Linoleic Acid; Magnetic Resonance Spectroscopy; Neoplasms; Oxidation-Reduction; Picrates; Reactive Oxygen Species; Spectrophotometry, Infrared

Polyunsaturated fatty acids (PUFAs) have been reported to play a regulatory role in tumour growth progression. In the present study, we have synthesized ester derivatives of two important PUFA viz., linoleic acid (LA) and arachidonic acid (AA) with propofol, a widely used general anaesthetic-sedative agent. The novel propofol ester analogues have been found to inhibit various cancer cell lines in a dose-dependent manner. Moreover, the compounds have been found to induce apoptotic cell death by enhancing the release of cytochrome c and expression of caspase-3. The data of the present study suggest that novel propofol-PUFA esters have strong potential to emerge as effective anticancer agents.

Topics: Antineoplastic Agents; Apoptosis; Arachidonic Acid; Caspase 3; Cell Line, Tumor; Esters; Fatty Acids, Unsaturated; Humans; Hypnotics and Sedatives; Linoleic Acid; Neoplasms; Propofol

Topics: Adult; Aged; Aged, 80 and over; alpha-Linolenic Acid; Animals; Arachidonic Acid; Coronary Artery Disease; Coronary Disease; Diet; Dietary Fats; Fatty Acids; Fatty Acids, Omega-3; Fatty Acids, Omega-6; Greece; Humans; Japan; Linoleic Acid; Lipids; Male; Middle Aged; Neoplasms; Risk Factors; Stroke; United States

Topics: Adult; Aged; Aged, 80 and over; Animals; Anticarcinogenic Agents; Austria; Carcinogens; Cholesterol, Dietary; Dietary Fats; Fatty Acids, Omega-3; Fatty Acids, Omega-6; France; Humans; Japan; Linoleic Acid; Middle Aged; Neoplasms; Netherlands; United States

Pectin was dissolved in deionized distilled water (2%, vol/vol) and irradiated at 20 kGy using a Co-60 gamma ray irradiator. The resulting solution was dialyzed and lyophilized. The samples were separated into three groups to estimate their antioxidant and cancer cell proliferation effects: non-irradiated (0 kGy), irradiated (20 kGy), and dialyzed (20 kGy-F, mol wt <10,000) samples. Antioxidant properties of each treatment was tested by a beta-carotene-linoleic acid bleaching assay and electron donating ability and compared for antioxidant index, which indicated that the activity was higher in the order of 20 kGy-F > 20 kGy > 0 kGy. Spleen cell survival effect of the irradiated pectin (20 kGy) and dialyzed (20 kGy-F) samples was higher than the non-irradiated control (0 kGy). The pectins inhibited growth of the cancer cell in the order of 20 kGy- F > 20 kGy > 0 kGy. The Ames test revealed that none of the fractions was mutagenic, and there was no indication of a dose-dependent response for any of the samples. These results suggest that a functional pectin oligosaccharide can be produced by irradiation for the food industry without any chemical treatment.

Topics: Antioxidants; beta Carotene; Biphenyl Compounds; Cell Division; Cell Line, Tumor; Citrus; Free Radical Scavengers; Fruit; Gamma Rays; Humans; Linoleic Acid; Mutagenicity Tests; Neoplasms; Oligosaccharides; Oxidation-Reduction; Pectins; Picrates

Dietary and serum fatty acid composition has been implicated in the pathogenesis of prostate and other cancers, but findings have been conflicting. Cohort studies reporting serum fatty acid composition are lacking. We assessed the association of fatty acid composition determined from dietary records and serum with incident cancer of the prostate and any site in a population-based cohort of 2,002 middle-aged Finnish men who were free of cancer at baseline and during the first 4 years of follow-up. During 12.6 years of follow-up, 46 men developed prostate cancer and 151 any cancer. Men with proportions of serum nonesterified [risk ratio (RR) 0.28; 95% confidence intervals (CI) 0.12-0.66] and esterified linoleic acid (RR 0.37; 95% CI = 0.16-0.86) and total polyunsaturated fatty acids (RR 0.30; 95% CI = 0.12-0.71) in the upper third were less than 1/3 as likely to develop prostate cancer during follow-up. Adjustment for possible confounders like socioeconomic status, physical activity, obesity and insulin concentrations did not attenuate the association. Similar but weaker associations with any cancer were found. Dietary linoleic acid intake also tended to be inversely associated with incident prostate cancer (age-adjusted RR for the upper vs. lower third 0.55; 95% CI = 0.26-1.14, p for the trend 0.097). Substitution of linoleic acid for saturated fat in middle-aged men consuming a high saturated-fat diet may decrease the risk of prostate and other cancers, although it is possible that some of the effect may be mediated by nutrients closely associated with vegetable fats.

Topics: Blood Glucose; Cohort Studies; Fatty Acids, Nonesterified; Fatty Acids, Unsaturated; Follow-Up Studies; Humans; Incidence; Linoleic Acid; Male; Middle Aged; Neoplasms; Prostatic Neoplasms; Risk; Risk Factors; Smoking; Time Factors

Vegetables and fruits have been shown to be good sources of antioxidants. Benincasa hispida (wax gourd) has been used in traditional Chinese medicine to treat hypertension and inflammation. The aims of this study were to investigate the abilities of antioxidation and inhibition of angiotensin-converting enzyme (ACE) activity of wax gourd pulp, core, seed, and peel prepared by different extraction methods. The fresh weights required to reach 50% inhibition of linoleic acid oxidation were higher in fresh extracts, compared to other extraction methods. Fresh weights required to reach 50% inhibition were the lowest in seed. The seed had the lowest Cu2+ -induced low-density lipoprotein (LDL) oxidation percentage and inhibition level of ACE activity among all parts. The higher antioxidant capacity of the seed may result from the higher total phenolics contents and superoxide dismutase activity. The abilities of antioxidation and ACE activity inhibition may provide protective effects against cardiovascular diseases and cancers.

Topics: Angiotensin-Converting Enzyme Inhibitors; Antioxidants; Cardiovascular Diseases; Cucurbitaceae; Humans; Linoleic Acid; Lipoproteins, LDL; Neoplasms; Oxidation-Reduction; Phenols; Plant Extracts; Seeds; Superoxide Dismutase

Both n-6 and n-3 polyunsaturated fatty acids are dietary fats important for cell function, being involved in several physiologic and pathologic processes, such as tumorigenesis. Linoleic acid and conjugated linoleic acid, its geometrical and positional stereoisomer, were tested on several human tumor cell lines originating from different tissues and with different degrees of malignancy. This was to provide the widest possible view of the impact of dietary lipids on tumor development. While linoleic acid exerted different effects, ranging from inhibitory to neutral, even promoting growth, conjugated linoleic acid inhibited growth in all lines tested and was particularly effective against the more malignant cells, with the exception of mammary tumor cells, in which behavior was the opposite, the more malignant cell line being less affected. The inhibitory effect of conjugated linoleic acid on growth may be accompanied by different contributions from apoptosis and necrosis. The effects of conjugated linoleic acid on growth or death involved positive or negative variations in PPARs. The important observation is that a big increase of PPARalpha protein occurred in cells undergoing strong induction of apoptosis, whereas PPARbeta/delta protein decreased. Although PPARalpha and PPARbeta/delta seem to be correlated to execution of the apoptotic program, the modulation of PPARgamma appears to depend on the type of tumor cell, increasing as protein content, when inhibition of cell proliferation occurred. In conclusion, CLA may be regarded as a component of the diet that exerts antineoplastic activity and its effect may be antiproliferative or pro-apoptotic.

Topics: Antineoplastic Agents; Apoptosis; Breast Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Cell Line, Tumor; Cell Proliferation; Female; Gene Expression Regulation, Neoplastic; Glioblastoma; Humans; Linoleic Acid; Linoleic Acids, Conjugated; Liver Neoplasms; Necrosis; Neoplasms; Peroxisome Proliferator-Activated Receptors; PPAR alpha; PPAR delta; PPAR gamma; PPAR-beta; Urinary Bladder Neoplasms

Modifying effects of dietary administration of conjugated fatty acids from safflower oil (CFA-S), rich in conjugated linoleic acid, on major organs were examined in the post-initiation stage of a two-stage carcinogenesis model in female rats. Groups of 21 or 22 F344 female rats were treated sequentially with 2,2'-dihydroxy-di-n-propylnitosamine (intragastrically, i.g.), 7,12-dimethylbenz[a]anthracene (i.g.), 1,2-dimethylhydrazine (subcutaneously) and N-butyl-N-(4-hydroxybutyl)nitrosamine (in drinking water) during the first 3 weeks for initiation, and then administered diet containing 1 or 0.1% CFA-S for 33 weeks. Further groups of animals were treated with carcinogens or 1% CFA-S alone, or maintained as non-treated controls. All surviving animals were killed at week 36, and major organs were examined histopathologically for development of pre-neoplastic and neoplastic lesions. The 1 and 0.1% CFA-S treatment significantly decreased the incidence and multiplicity of mammary carcinomas, though a clear dose response was not observed. In the urinary bladder, the incidence of papillary or nodular hyperplasia but not tumors was significantly increased in the 1% CFA-S-treated group. The results indicate that low dose CFA-S may find application as a potent chemopreventor of mammary carcinogenesis.

Topics: 1,2-Dimethylhydrazine; 9,10-Dimethyl-1,2-benzanthracene; Animals; Body Weight; Butylhydroxybutylnitrosamine; Carcinogens; Dietary Supplements; Dose-Response Relationship, Drug; Fatty Acids; Female; Glutathione Transferase; Hyperplasia; Linoleic Acid; Mammary Neoplasms, Experimental; Neoplasms; Nitrosamines; Organ Size; Phosphorylation; Rats; Rats, Inbred F344; Rats, Sprague-Dawley; Safflower Oil; Time Factors; Urinary Bladder Neoplasms

In animal or cell culture studies, the growth and spread of cancer can be slowed by many nutrients, food factors, herbal extracts, and well-tolerated, available drugs that are still rarely used in the clinical management of cancer, in part because they seem unlikely to constitute definitive therapies in themselves. However, it is reasonable to expect that mechanistically complementary combinations of these measures could have a worthwhile impact on survival times and, when used as adjuvants, could improve the cure rates achievable with standard therapies. The therapeutic options available in this regard include measures that: down-regulate serum free IGF-I; suppress the synthesis of mevalonic acid and/or certain derivatives thereof; modulate arachidonate metabolism by inhibiting 5-lipoxygenase, 12-lipoxygenase, or COX-2; antagonize the activation of AP-1 transcription factors; promote the activation of PPAR-gamma transcription factors; and that suppress angiogenesis by additional mechanisms. Many of these measures appear suitable for use in cancer prevention.

Topics: Animals; Arachidonic Acid; Biological Factors; Cell Division; Down-Regulation; Flavonoids; Humans; Insulin-Like Growth Factor I; Linoleic Acid; Mevalonic Acid; Neoplasms; Neovascularization, Pathologic; Phenols; Phytotherapy; Plants; Polymers; Polyphenols; Receptors, Cytoplasmic and Nuclear; Selenium; Transcription Factors

E-cadherin is a cell to cell adhesion molecule which acts as a suppressor of metastasis. This study examined the effect of gamma-linolenic acid (GLA), a n-6 polyunsaturated fatty acid, on the expression of E-cadherin in human cancer cells. Western blotting studies demonstrated that treatment of cells with GLA for 24 h increased the expression of E-cadherin in lung, colon, breast, melanoma, and liver cancer cells, but not in endothelial cells and fibroblasts. The results were confirmed by immunocytochemistry. In contrast, two other n-6 fatty acids, linoleic acid and arachidonic acid, failed to induce these changes. The increased expression of E-cadherin was correlated with reduced in vitro invasion and increased aggregation, indicating that the increased E-cadherin expression induced by GLA was biologically active. These data add GLA to the short list of E-cadherin up-regulatory factors. The up-regulation of E-cadherin expression in human cancer cells may contribute to the anticancer properties of GLA.

Topics: Antineoplastic Agents; Arachidonic Acid; Blotting, Western; Cadherins; Cell Aggregation; gamma-Linolenic Acid; Humans; Immunohistochemistry; Linoleic Acid; Linoleic Acids; Neoplasm Invasiveness; Neoplasms; Tumor Cells, Cultured

This hypothesis proposes that the essential fatty acids (EFAs), linoleic acid (LA) and gamma-linolenic acid (GLA), play important roles in cancer treatment. Oxidation of LA by lipoxidase especially increases tumour cell death, whilst GLA inhibits urokinase-type plasminogen activator (uPA) activity. Increased uPA activity is: firstly, responsible for cancer invasion and metastasis and secondly, responsible for proteolysis of lipoxidase which favours a decrease in cancer cell death. Addition of LA and GLA to available therapeutic regimens may be worth considering in cancer treatment.

Topics: Antineoplastic Agents, Phytogenic; Cell Death; Fatty Acids, Essential; gamma-Linolenic Acid; Humans; Linoleic Acid; Linoleic Acids; Lipoxygenase; Models, Biological; Neoplasm Invasiveness; Neoplasm Metastasis; Neoplasm Proteins; Neoplasms; Oxidation-Reduction; Plant Oils; Urokinase-Type Plasminogen Activator

There are numerous anticarcinogens in the diet. An important question is how to use such substances in an effective, directed way to reduce cancer risk in humans. The "designer foods" concept is one approach for accomplishing this goal. Foods would be engineered to contain effective levels of anticarcinogens. This idea will work only to the extent that there is sufficient scientific knowledge on which to base such food design. Obviously, it is not sufficient simply to extrapolate from animal data to humans. A hypothetical example of the possible "designer fat substitute" is presented and discussed.

Topics: Diet, Reducing; Energy Intake; Fat Substitutes; Humans; Linoleic Acid; Linoleic Acids; Neoplasms; Proteins

We have previously shown that cis-unsaturated fatty acids (c-UFAs) possess a selective tumoricidal action that can be blocked by antioxidants. This property of c-UFAs might be due to various factors, including increased uptake, unusual distribution, or an ability to alter free radical generation in tumor but not normal cells. 14C-labelled linoleic acid (LA) uptake was almost the same in normal and tumor cells, whereas that of 14C-labelled arachidonic acid (AA) and 14C-labelled eicosapentaenoic acid (EPA) in tumor cells was substantially less than in normal cells. Tumor cells incorporate major portions of the fatty acids in the ether lipid and phospholipid fractions, whereas normal cells incorporate the fatty acids primarily in the phospholipid fraction. LA, AA, and EPA augmented nitroblue tetrazolium reduction, an indication of free radical generation, selectively in the tumor cells. These results suggest that there are significant differences between normal and tumor cells in fatty acid uptake and distribution, and in the ability of fatty acids to generate free radicals.

Topics: Animals; Arachidonic Acid; Arachidonic Acids; Biological Transport, Active; Cell Line; Eicosapentaenoic Acid; Fatty Acids, Unsaturated; Free Radicals; Humans; Linoleic Acid; Linoleic Acids; Neoplasms; Nitroblue Tetrazolium; Oxidation-Reduction

To test the influence of changes in membrane fatty acid composition on the radiation response of mammalian cells, human LDV cells were cultured in medium containing delipidated serum supplemented with either oleic or linoleic acid. Analysis of lipid extracts of the cells by gas liquid chromatography showed that, after 3 or more days growth in oleic or linoleic acid supplemented media, there were substantial overall increases in the proportion of oleate and linoleate, respectively, in the cellular lipid. Smaller absolute changes were measured in nuclear phospholipid, which was found to be low in unsaturated phospholipid compared to the rest of the cell. Fluorescence polarization measurements using diphenylhexatriene indicated an increased membrane fluidity in cells grown in the presence of excess linoleic acid and to a lesser extent for oleic acid. The clonogenic capacity of the cells after irradiation in air or nitrogen was not altered by any of these membrane compositional changes. The lack of effect on radiation sensitivity, in contrast to that reported for bacteria (E. coli K1060), is consistent with the fact that little or no change was brought about in the nuclear membrane composition, since evidence from partial cell irradiation experiments indicates that the cell nucleus is the sensitive target for cell killing by ionizing radiation. The ability of the cell to maintain a low level of unsaturated phospholipids in its nuclear membrane may be an important general defence mechanism against free radical damage to chromatin mediated by lipid peroxidation.

Topics: Cell Division; Cell Line; Cell Membrane; Cell Survival; Fatty Acids; Humans; Linoleic Acid; Linoleic Acids; Membrane Fluidity; Membrane Lipids; Neoplasms; Nuclear Envelope; Oleic Acid; Oleic Acids

Topics: Body Fluids; Chromatography; Exudates and Transudates; Fatty Acids; Heart Failure; Linoleic Acid; Lipids; Neoplasms; Oleic Acid; Palmitic Acid; Peritoneum; Pleural Effusion; Stearic Acids

Topics: Cholesterol; Female; Glycerides; Humans; Linoleic Acid; Lipids; Neoplasms; Ovarian Neoplasms; Steroids

Topics: Arachidonic Acid; Humans; Linoleic Acid; Lipid Metabolism; Neoplasms; Phospholipids; Sarcoma

Topics: Linoleic Acid; Neoplasms; Sarcoma; Sarcoma, Experimental

Topics: Animals; Ascites; Biochemical Phenomena; Carbohydrate Metabolism; Carbohydrates; Carcinoma, Ehrlich Tumor; Linoleic Acid; Lipid Metabolism; Neoplasms