linoleic-acid and Prostatic-Neoplasms

The role of dietary fatty acids on cancer is still controversial. To examine the current literature on the protective role of conjugated linoleic acid (CLA) and marine long-chain fatty acids [eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] and the risk of breast and prostate cancer, data from 41 case-control and cohort studies and relevant in vitro and animal experiments were included in this 2000-2010 revision. Epidemiological studies on CLA intake or its tissue concentration related to breast and prostate tumorigenesis are not conclusive; EPA and DHA intake have shown important inverse associations just in some studies. Additional research on the analysed association is required.

Topics: Breast Neoplasms; Dietary Fats; Docosahexaenoic Acids; Eicosapentaenoic Acid; Female; Humans; Linoleic Acid; Linoleic Acids, Conjugated; Male; Prostatic Neoplasms

This study reviews epidemiological works having studied the associations of dietary fatty acids, especially of n-6 or n-3 polyunsaturated fatty acids (PUFA), with the risks of colorectal and prostate cancers.. The epidemiological studies reviewed were those having tested the association of colorectal and prostate cancer risk with the dietary intake or the blood or adipose tissue levels of fatty acids, especially of n-6 and n-3 PUFA, and with the dietary intake of fish and seafood.. Most studies based on a dietary questionnaire did not find any association of the risk of colorectal cancer with the consumption of either total fatty acids or any particular fatty acid, after adjustment for total energy intake had been made. A few studies suggest that trans fatty acid consumption could increase colorectal cancer risk. Most studies based either on a dietary questionnaire or on biomarkers, did not find any association of total, saturated or monounsaturated fatty acid, as well as of linoleic or arachidonic acids, with prostate cancer risk, after adjustment for total energy intake. Most studies failed to find an association of prostate cancer risk with fish or long-chain n-3 PUFA intake, but recent cohort studies did find an inverse association of fish consumption with the risk of the latest stages of prostate cancer. In contrast, alpha-linolenic acid intake was associated with an increase of prostate cancer risk in a majority of epidemiological studies, but other studies did not find this association. This latter point might be of concern, and needs to be clarified by other results, especially those of ongoing prospective studies.

Topics: alpha-Linolenic Acid; Animals; Colorectal Neoplasms; Dietary Fats; Fatty Acids; Fatty Acids, Omega-3; Fatty Acids, Omega-6; Fishes; Humans; Linoleic Acid; Male; Prostatic Neoplasms; Trans Fatty Acids

Experiments in animal models of mammary carcinogenesis suggest that fatty acids promote mammary tumors development. This effect depends first on the amount then on the type of fatty acids available. n-6 fatty acids such as linoleic acid generally stimulates mammary tumor growth, while n-3 fatty acids oppose this effect. Conjugated diene fatty acids (CLA) inhibit mammary carcinogenesis when brought at elevated amount. There are limitations in using an animal model in the analysis between nutrition and colorectal cancers. This is ascribable to the following: firstly, the digestive tract of rodents if different from that of humans and secondly, the induction of colon cancer in these animals (chemical carcinogenesis, injection of cancerous cells or transgenesis) does not mimic human colon carcinogenesis. However, on the basis of numerous published data, some important correlations have arisen that could generate hypotheses and guide new epidemiological/interventional and experimental studies. In these animal models it appears that an adequate supply of n-3 PUFAs and oleic acid in food may exert a protective effect at all stages of colon carcinogenesis. On the other hand, an excessive consumption of n-6 PUFAs and of saturated fatty acids could promote colon cancers.

Topics: alpha-Linolenic Acid; Animals; Colonic Neoplasms; Dietary Fats; Dietary Fats, Unsaturated; Fatty Acids; Fatty Acids, Omega-3; Fatty Acids, Omega-6; Fatty Acids, Unsaturated; Female; Fish Oils; Humans; Linoleic Acid; Male; Mammary Neoplasms, Experimental; Models, Animal; Neoplasm Transplantation; Neoplasms, Experimental; Oleic Acid; Prostatic Neoplasms; Rodentia

Several studies have examined the association between polyunsaturated fatty acids and prostate cancer risk. We evaluated the evidence on the association between the essential polyunsaturated fatty acid, known as alpha-linolenic acid, and the risk of prostate cancer in humans.. We comprehensively reviewed published studies on the association between alpha-linolenic acid and the risk of prostate cancer using MEDLINE.. A number of studies have shown a positive association between dietary, plasma or red blood cell levels of alpha-linolenic acid and prostate cancer. Other studies have demonstrated either no association or a negative association. The limitations of these studies include the assumption that dietary or plasma alpha-linolenic acid levels are positively associated with prostate tissue alpha-linolenic acid levels, and measurement errors of dietary, plasma and red blood cell alpha-linolenic acid levels.. More research is needed in this area before it can be concluded that there is an association between alpha-linolenic acid and prostate cancer.

Topics: Biomedical Research; Fatty Acids, Unsaturated; Humans; Linoleic Acid; Male; Prostatic Neoplasms; Risk Factors

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

Linoleic acid, an n-6 polyunsaturated fatty acid, is essential for normal mammary tissue development, at least in part because it provides the metabolic precursor required for the biosynthesis of key eicosanoids. A similar requirement applies to the growth of estrogen-independent but apparently not to estrogen-dependent rodent mammary and human breast carcinoma cells in vitro. By way of lipoxygenase products, n-6 fatty acids also regulate expression of the invasive phenotype. High-fat, linoleic acid-rich diets promote chemically induced rat mammary carcinogenesis, virally induced mouse mammary tumor development, and the growth and metastasis of estrogen-independent human breast cancer cells in athymic nude mice. In contrast, saturated fatty acids have no discernible effects on mammary carcinogenesis or progression. Most mechanistic studies have focused on the cyclooxygenase and lipoxygenase products of n-6 fatty acid metabolism, and support is accumulating for interactions between these eicosanoids and growth factors and oncogenes. The investigation of dietary fatty acids in prostate cancer is at an early stage and has been handicapped by a lack of satisfactory animal models. However, there are indications that the n-6 fatty acids perform functions in experimental prostate cancer progression similar to those described for breast cancer.

Topics: Animals; Dietary Fats; Eicosanoids; Fatty Acids, Omega-6; Fatty Acids, Unsaturated; Female; Humans; Linoleic Acid; Male; Mammary Neoplasms, Experimental; Prostatic Neoplasms; Tumor Cells, Cultured

Although international comparisons have suggested positive associations between consumption of total or saturated fat and risk of breast cancer, these relations have not been supported in large prospective studies in which confounding factors were minimized. There is no suggestion from international comparisons, case-control, or cohort studies that monounsaturated fat (the most abundant fat in the US diet) increases risk of breast cancer, and there is some evidence that higher intake, particularly in the form of olive oil, might actually reduce risk. The available epidemiologic evidence provides little support for any important relation between intake of either linoleic acid or extra-long-chain n-3 fatty acids from fish and risk of breast cancer. However, high consumption of linoleic acid is a relatively recent phenomenon in Western societies and continued evaluation of its relation with breast cancer risk is warranted because of animal data suggesting possible adverse effects. Ecologic, case-control, and cohort studies all support a positive relation between consumption of animal fat and risk of prostate cancer, but current evidence suggests that vegetable fat is not related to risk of this cancer. Although relevant data are limited, neither linoleic acid nor extra-long-chain n-3 fatty acid consumption appears to be related to risk of prostate cancer. Because of the strong evidence that some aspect of foods high in animal fat increases risk of prostate cancer, further studies of specific dietary fatty acids in relation to the occurrence of this malignancy are likely to be particularly valuable.

Topics: Animals; Breast Neoplasms; Diet; Epidemiologic Studies; Fatty Acids, Omega-3; Female; Humans; Linoleic Acid; Male; Prostatic Neoplasms; Risk Factors

Previous studies suggest a positive association between markers of trans-fatty acid intake and prostate cancer. We therefore prospectively evaluated the association between blood trans-fatty acid levels and risk of prostate cancer.. We conducted a nested case-control study among 14,916 apparently healthy men who provided blood samples in 1982. Blood fatty acid levels were determined for 476 men diagnosed with prostate cancer during a 13-year follow-up and their matched controls. Controls were individually matched to cases according to age and smoking status at baseline. Conditional logistic regression was used to estimate the relative risk and 95% confidence interval of total, nonaggressive (stage A/B and low grade), and aggressive (stage C/D, high grade, subsequent distant metastasis or death) prostate cancer associated with blood levels of specific trans-fatty acids.. Blood levels of all the trans-fatty acids examined were unrelated to total prostate cancer risk. When results were divided according to tumor aggressiveness, blood levels of 18:1n-9t, all the 18:2t examined, and total trans-fatty acids were positively associated to nonaggressive tumors. The relative risks (95% confidence intervals; P trend) comparing top with bottom quintile trans-fatty acid levels were 2.16 (1.12-4.17; 0.11) for 18:1n-9t, 1.97 (1.03-3.75; 0.01) for total 18:2t, and 2.21 (1.14-4.29; 0.06) for total trans-fatty acids. None of the trans fats examined was associated with aggressive prostate tumors.. Blood levels of trans isomers of oleic and linoleic acids are associated with an increased risk of nonaggressive prostate tumors. As this type of tumors represents a large proportion of prostate cancer detected using prostate-specific antigen screening, these findings may have implications for the prevention of prostate cancer.

Topics: Aged; Aged, 80 and over; Case-Control Studies; Humans; Linoleic Acid; Male; Middle Aged; Oleic Acid; Prospective Studies; Prostatic Neoplasms; Risk Factors; Surveys and Questionnaires; United States

Hypoxia is a well-established feature of prostate cancer (PCa) and is associated with disease aggressiveness. The hypoxic microenvironment initiates multiple adaptive responses including epithelial-to-mesenchymal transition (EMT) and a remodeling of calcium homeostasis involved in cancer progression. In the present study, we identified a new hypoxia signaling pathway with a positive feedback loop between the EMT transcription factor Zeb1 and SK3, a Ca

Topics: Cell Line, Tumor; Cell Movement; Eicosapentaenoic Acid; Epithelial-Mesenchymal Transition; Glycolipids; Humans; Hypoxia; Linoleic Acid; Male; Prostatic Neoplasms; Small-Conductance Calcium-Activated Potassium Channels; Tumor Microenvironment; Zinc Finger E-box-Binding Homeobox 1

Genetic and nutritional factors have been linked to the risk of aggressive prostate cancer (PCa). The fatty acid (FA) composition of peri-prostatic adipose tissue (PPAT), which reflects the past FA intake, is potentially involved in PCa progression. We analysed the FA composition of PPAT, in correlation with the ethno-geographical origin of the patients and markers of tumour aggressiveness.. From a cohort of 1000 men treated for PCa by radical prostatectomy, FA composition of PPAT was analysed in 156 patients (106 Caucasians and 50 African-Caribbeans), 78 with an indolent tumour (ISUP group 1 + pT2 + PSA <10 ng/mL) and 78 with an aggressive tumour (ISUP group 4-5 + pT3). The effect of FA extracted from PPAT on in-vitro migration of PCa cells DU145 was studied in 72 patients, 36 Caucasians, and 36 African-Caribbeans.. FA composition differed according to the ethno-geographical origin. Linoleic acid, an essential n-6 FA, was 2-fold higher in African-Caribbeans compared with Caucasian patients, regardless of disease aggressiveness. In African-Caribbeans, the FA profile associated with PCa aggressiveness was characterised by low level of linoleic acid along with high levels of saturates. In Caucasians, a weak and negative association was observed between eicosapentaenoic acid level (an n-3 FA) and disease aggressiveness. In-vitro migration of PCa cells using PPAT from African-Caribbean patients was associated with lower content of linoleic acid.. These results highlight an important ethno-geographical variation of PPAT, in both their FA content and association with tumour aggressiveness.

Topics: Adipose Tissue; Aged; Black People; Cell Line, Tumor; Cell Movement; Databases, Factual; Eicosapentaenoic Acid; Fatty Acids; France; Humans; Linoleic Acid; Male; Middle Aged; Neoplasm Invasiveness; Paracrine Communication; Prostatectomy; Prostatic Neoplasms; Signal Transduction; West Indies; White People

In this study, we developed a rapid strategy to screen a serum-free medium for culturing the anchorage-dependent PC-3 prostate cancer cells, which was going to be prepared in large scale to generate GM-CSF/TNFα-surface-modified whole cell prostate cancer vaccine. Automated real-time cellular analysis as a rapid and non-invasive technology was used to monitor the growth of PC-3 cells in 16-well plates. At the same time, Plackett-Burman design was employed to identify the most influential formulation by integrating relevant information statistically. The effects of the 16 selected factors were evaluated during exponential cell growth and three medium constituents (EGF, FGF and linoleic acid) were identified to have significant effects on the cell growth. Subsequently, the response surface methodology with central composite design was applied to determine the interactions among the three factors so that these factors were optimized to improve cell growth. Finally, the prediction of the best combination was made under the maximal response to optimize cell growth by Design-Expert software 7.0. A total of 20 experiments were conducted to construct a quadratic model and a second-order polynomial equation. With the optimized combination validated by the stability test of serial passaging PC-3 cells, the serum-free medium had similar cell density and cell viability to the original serum medium. In summary, this high-throughput scheme minimized the screening time and may thus provide a new platform to efficiently develop the serum-free media for adherent cells.

Topics: Cancer Vaccines; Cell Adhesion; Cell Culture Techniques; Cell Line, Tumor; Cell Proliferation; Cell Survival; Computer Systems; Culture Media, Serum-Free; Epidermal Growth Factor; Fibroblast Growth Factors; High-Throughput Screening Assays; Humans; Linoleic Acid; Male; Prostatic Neoplasms; Software

Epidemiological data suggest that omega-6 (ω-6) fatty acids (FAs) may be associated with cancer incidence and/or cancer mortality, whereas ω-3 FAs are potentially protective. We examined the association of the ratio of ω-6 to ω-3 FA (ω-6:ω-3) and individual FA components with pathological results among men with prostate cancer (PCa) undergoing radical prostatectomy.. Sixty-nine men were included in the study. Components of ω-6 (linoleic acid (LA), arachidonic acid (AA), and dihomo-γ-linolenic acid (DGLA)) and ω-3 (docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA)) were analyzed by liquid chromatography/mass selective detector separation. Logistic regression analysis was performed to determine association of FA with pathological high grade (Gleason ≥4+3) disease.. The were 35 men with low grade disease (Gleason ≤3+4) and 34 men with high grade disease. Men with low grade disease were significantly younger (58y vs 61y, p = 0.012) and had lower D'Amico clinical classification (p = 0.001) compared to men with high grade disease. There was no significant association of ω-6:ω-3 with high grade disease (OR 0.93, p = 0.78), however overall ω-6, ω-3, and individual components of ω-6 and ω-3 FAs except EPA were significantly associated with high grade disease (ω-6: OR 3.37, 95% CI: 1.27,8.98; LA: OR 3.33, 95% CI:1.24,8.94; AA: OR 2.93, 95% CI:1.24,6.94; DGLA: OR 3.21, 95% CI:1.28,8.04; ω-3: OR 3.47, 95% CI:1.22,9.83; DHA: OR 3.13, 95% CI:1.26,7.74). ω-6 and ω-3 FA components were highly correlated (Spearman ρ = 0.77).. Higher levels of individual components of ω-6 and ω-3FAs may be associated with higher-grade PCa.. Studies into the causative factors/pathways regarding FAs and prostate carcinogenesis may prove a potential association with PCa aggressiveness.

Topics: 8,11,14-Eicosatrienoic Acid; Aged; Arachidonic Acid; Chromatography, High Pressure Liquid; Docosahexaenoic Acids; Eicosapentaenoic Acid; Fatty Acids, Omega-3; Fatty Acids, Omega-6; Humans; Linoleic Acid; Male; Mass Spectrometry; Middle Aged; Neoplasm Grading; Odds Ratio; Prostatectomy; Prostatic Neoplasms

Animal and experimental studies have demonstrated that long-chain n-3 fatty acids inhibit the development of prostate cancer, whereas n-6 fatty acids might promote it. We performed a case-cohort analysis within the Melbourne Collaborative Cohort Study using a random sample of 1,717 men and 464 prostate cancer cases to investigate associations between fatty acids assessed in plasma phospholipids (PPLs) or diet (estimated using a 121-item food frequency questionnaire) and prostate cancer risk. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox regression. Prostate cancer risk was positively associated with %PPL saturated fatty acids (SFAs); HR [95% CI] = 1.51 [1.06, 2.16] (Q5 vs. Q1, fifth vs. first quintile); p-trend = 0.003. HRs (Q5 to Q2 vs. Q1) were significantly elevated for %PPL palmitic acid. %PPL oleic acid was inversely associated with risk, HR = 0.62 [0.43, 0.91] (Q5 vs. Q1); p-trend = 0.04. No statistically significant linear trends were observed for dietary intakes. The HRs were elevated for moderate intakes of linoleic acid (Q2 and Q3 vs. Q1, 1.58 [1.10, 2.28] and 1.70 [1.18, 2.46], respectively), but the increase was not significant for higher intakes (Q4 and Q5). No association varied significantly by tumour aggressiveness (all p-homogeneity > 0.1). Prostate cancer risk was positively associated with %PPL SFA, largely attributable to palmitic acid and inversely associated with %PPL monounsaturated fatty acids, largely attributable to oleic acid. Higher risks were also observed for dietary n-6 polyunsaturated fats, primarily linoleic acid.

Topics: Adult; Aged; Aged, 80 and over; Case-Control Studies; Cohort Studies; Diet; Dietary Fats; Fatty Acids; Fatty Acids, Monounsaturated; Fatty Acids, Omega-6; Female; Humans; Linoleic Acid; Male; Middle Aged; Oleic Acid; Palmitic Acid; Phospholipids; Prospective Studies; Prostatic Neoplasms; Risk Factors; Surveys and Questionnaires

α-Lactalbumin α-La), together with oleic acid can be converted to a complex, which kills tumor cells selectively. Cytotoxic α-La -oleic acid and α-La -linoleic acid complexes were generated by adding fatty acid to camel holo α-La at 60 ° C (referred to as La-OA-60 and La-LA-60 state, respectively). Structural properties of these complexes were studied and compared to the camel α-La. The experimental results show that linoleic acid induces α-La partial unfolding but oleic acid does not change the protein structure significantly. Also the stability of La-OA-60 and La-LA-60 toward thermal denaturation was measured. The order of temperature at the transition midpoint is as follows: La-LA-60 < La-OA-60 < α-La. La-OA-60 complex inhibited tubulin polymerization in vitro. Although the structures of La-OA-60 and La-LA-60 were different, these two complexes had similar cytotoxic effect to DU145 human prostate cancer cells. Samples of La-OA-60 that have been renatured after denaturation lost the specific biological activity toward tumor cells.

Topics: Antineoplastic Agents; Calcium; Cell Line, Tumor; Circular Dichroism; Computer-Aided Design; Drug Design; Drug Discovery; Hot Temperature; Humans; Lactalbumin; Linoleic Acid; Male; Oleic Acid; Prostatic Neoplasms; Protein Conformation; Protein Folding; Protein Stability; Protein Structure, Secondary; Spectrometry, Fluorescence; Tubulin

Hormone ablation therapy typically causes regression of prostate cancer and represents an important means of treating this disease, particularly after metastasis. However, hormone therapy inevitably loses its effectiveness as tumors become androgen-independent, and this conversion often leads to death because of subsequent poor responses to other forms of treatment. Because environmental factors, such as diet, have been strongly linked to prostate cancer, we examined the affects of dietary polyunsaturated fatty acids (PUFAs; at 1.5 wt%) on growth of androgen-dependent (CWR22) and androgen-independent (CWR22R) human prostatic cancer xenografts, the acute response of CWR22 tumors to ablation therapy, and their progression to androgen independence. Significant diet-induced changes in tumor n-3 or n-6 PUFA content had no affect on CWR22 or CWR22R tumors growing with or without androgen support, respectively. However, dietary changes that increased tumor eicosapentaenoic acid and linoleic acid content enhanced responses to ablation therapy, measured by cancer cell apoptosis and mitosis. In addition, relapse to androgen-independent growth (measured by renewed increases in tumor volume and serum prostate-specific antigen after ablation) positively correlated with tumor arachidonic acid content. There was no correlation between expression of 15-lipoxygenase isozymes or their products and tumor growth or responses to ablation. In conclusion, dietary n-3 PUFA may enhance the response of prostate cancer to ablation therapy and retard progression to androgen-independent growth by altering tumor PUFA content.

Topics: Androgen Antagonists; Animals; Apoptosis; Arachidonic Acid; Blotting, Western; Dietary Fats, Unsaturated; Drug Resistance, Neoplasm; Eicosanoids; Eicosapentaenoic Acid; Fatty Acids, Unsaturated; Humans; Linoleic Acid; Male; Mice; Neoplasms, Hormone-Dependent; Oleic Acid; Prostatic Neoplasms; Reverse Transcriptase Polymerase Chain Reaction; Spectrometry, Mass, Electrospray Ionization; Xenograft Model Antitumor Assays

Peroxisome proliferator-activated receptor gamma (PPARgamma) ligands seem to induce anticancer effects on prostate cancer cells, but the mechanism is not clear. The effect of PPARgamma ligands omega-6 fatty acids and ciglitazone (2-15 microM)--on proliferation, and apoptosis of LNCaP, PC-3, DU145, CA-K and BPH-K cells was studied. PPARgamma ligands led to: (1) reduction of proliferation (20-50%) of all the studied cell lines, (2) stimulation of differentiation of prostate cancer cells through an increased expression (1.5-3-fold: LNCaP, DU145, BPH-K) or reexpression (PC-3, CA-K) of E-cadherin with parallel inhibition of N-cadherin expression (PC-3, CA-K) and (3) down-regulation (1-2-fold) of beta-catenin and c-myc expression. The selective PPARgamma antagonist GW9662 abolished the effect of those ligands on prostate cancer cells. These results suggest that inhibition of beta-catenin and in effect c-myc expression through activation of PPARgamma may help prostate cancer cells to restore several characteristics of normal prostate cells phenotype.

Topics: Anilides; Antineoplastic Agents; Apoptosis; beta Catenin; Cadherins; Cell Differentiation; Cell Line, Tumor; Gene Expression Regulation, Neoplastic; Humans; Linoleic Acid; Male; PPAR gamma; Prostatic Neoplasms; Proto-Oncogene Proteins c-myc; Thiazolidinediones

Linoleic acid was isolated from both the methanol extracts of proso and Japanese millet as a histone deacetylase inhibitor. It showed uncompetitive inhibitory activity toward histone deacetylase (IC(50)=0.51 mM) and potent cytotoxicity toward human leukemia K562 (IC(50)=68 microM) and prostate cancer LNCaP cells (IC(50)=193 microM). Millet containing linoleic acid might have anti-tumor activity.

Topics: Antineoplastic Agents; Cell Line, Tumor; Echinochloa; Enzyme Inhibitors; Female; Histone Deacetylase Inhibitors; Humans; Inhibitory Concentration 50; Leukemia; Linoleic Acid; Male; Plant Extracts; Prostatic Neoplasms

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

The incidence of prostate carcinoma is very low in Eastern countries, such as Japan, suggesting that life style conditions may play a crucial role in the development of this pathology. Dietary omega-6 polyunsaturated fatty acids, such as linoleic (LA) and arachidonic (AA) acids, have been shown to stimulate the proliferation of prostate cancer cells after being converted into 5-HETE by means of the 5-lipoxygenase (5-LOX) pathway. Blockade of 5-LOX activity has been proposed as an attractive target for the prevention of the mitogenic action of dietary fats on prostate cancer. The 5-LOX gene has been shown to carry a response element for the orphan nuclear receptor RORalpha (for its RORalpha1 isoform in particular) in its promoter region. We attempt to clarify whether activation of RORalpha might modulate the expression of 5-LOX, thus interfering with the mitogenic activity of fatty acids in prostate cancer cells. We show that in androgen-independent DU 145 prostate cancer cells, LA, AA and their metabolite 5-HETE exert a strong stimulatory action on cell proliferation. This effect is completely counteracted by the simultaneous treatment of the cells with a non redox inhibitor of 5-LOX activity. We then demonstrate that: i) RORalpha, and specifically its RORalpha1 isoform, is expressed in DU 145 cells; ii) activation of RORalpha, by means of the thiazolidinedione derivative CGP 52608 (the synthetic RORalpha activator), significantly reduces 5-LOX expression, both at mRNA (as evaluated by comparative RT-PCR) and at protein (as investigated by Western blot analysis) level (this was confirmed by the reduced activity of 5-LOX in CGP 52608 treated cells); and iii) the treatment of DU 145 cells with CGP 52608 completely abrogated the proliferative action of both LA and AA. These results have been confirmed in another androgen-independent prostate cancer cell line (PC3). Our data indicate that, by decreasing the expression of 5-LOX, activation of RORalpha might interfere with the mitogenic activity of fatty acids on prostate cancer. We have shown previously that CGP 52608 reduces the proliferation and the metastatic behavior of DU 145 cells. These observations indicate that the orphan nuclear receptor RORalpha might be considered as a molecular target for the development of new chemopreventive or chemotherapeutic strategies for prostate carcinoma.

Topics: Arachidonate 5-Lipoxygenase; Arachidonic Acid; Cell Division; Humans; Hydroxyeicosatetraenoic Acids; Linoleic Acid; Male; Neoplasms, Hormone-Dependent; Nerve Tissue Proteins; Nuclear Receptor Subfamily 1, Group F, Member 1; Prostatic Neoplasms; Protein Isoforms; Receptors, Cytoplasmic and Nuclear; Reverse Transcriptase Polymerase Chain Reaction; Thiazoles; Thiosemicarbazones; Trans-Activators; Tumor Cells, Cultured

An effect of fatty acids has been implicated in men with advanced-stage prostate carcinoma and in men who have died of the disease. To evaluate the influence of fatty acids in men with prostate carcinoma at earlier stages, the authors examined the relation between prostatic concentrations of fatty acids and locally advanced prostate carcinoma in men with clinically organ-confined disease.. Fatty acids were measured by capillary gas chromatography in fresh, nonmalignant prostate tissue specimens collected during surgery from 196 men undergoing radical prostatectomy for localized prostate carcinoma. Two-sided, two-sample Student t tests compared mean concentrations in men with extraprostatic disease (pT3-4N0-1M0) with control men with organ-confined disease. Logistic regression accounted for clinical stage, prostate-specific antigen level, Gleason sum, and other factors.. Percent total prostatic polyunsaturated fatty acid (PUFA) was found to be inversely associated with risk of locally advanced prostate carcinoma (n=52) (odds ratio [OR]=0.93, 95% confidence interval [95% CI], 0.87-0.99; P=0.035). Risk of seminal vesicle involvement accounted for this association (OR=0.86, 95% CI, 0.78-0.95; P=0.003). Percent omega-3 fatty acid (eicosapentanoic + docosahexanoic acids) and percent arachidonic acid also were found to be inversely related to the risk of seminal vesicle involvement (OR=0.52, 95% CI, 0.30-0.90; P=0.02; and OR=0.84, 95% CI,; 0.75-0.95; P=0.005, respectively).. Prostatic PUFA levels appear to influence the risk of locally advanced prostate carcinoma in men with clinically organ-confined disease. This association may be mediated through the immune system.

Topics: Aged; Arachidonic Acid; Fatty Acids, Omega-3; Fatty Acids, Unsaturated; Humans; Linoleic Acid; Male; Middle Aged; Prostatic Neoplasms

gamma-Tocopherol (gammaT), the predominant form of vitamin E in diets, but not alpha-tocopherol, the major vitamin E form in tissues and supplements, inhibits proliferation of prostate cancer cells (LNCaP and PC-3) and lung cancer cells (A549). In contrast, at similar concentrations, gammaT has no effect on normal prostate epithelial cells. Combinations of some vitamin E forms, such as gammaT and delta-tocopherol, exhibit additive or synergistic inhibitory effects. In this study, gammaT or its combination with delta-tocopherol induced apoptosis in androgen-sensitive prostate LNCaP, but not in androgen-resistant PC-3 cells, by the induction of cytochrome c release, activation of caspase 9 and caspase 3, cleavage of poly-ADP-ribose polymerase (PARP), and involvement of caspase-independent pathways. Myriocin and fumonisin B1, specific inhibitors of key enzymes (serine palmitoyltransferase and dihydroceramide synthase, respectively) in de novo synthesis of sphingolipids, significantly protected cells from gammaT-induced DNA fragmentation, cytochrome c release, PARP cleavage, and the formation of active caspase 3. Compared with vehicle-treated controls, gammaT treatment led to pronounced dihydroceramide and dihydrosphingosine accumulation, which preceded morphological and biochemical manifestations of apoptosis. In contrast, ceramide and shpingosine levels did not increase until day 3, when substantial cell death took place. Our study demonstrates that gammaT and mixed vitamin E forms induce cell death by interrupting the de novo sphingolipid pathway in a prostate cancer cell line. Thus, certain vitamin E forms may be valuable as anticancer agents.

Topics: Apoptosis; Arachidonic Acid; Caspases; Cell Line, Tumor; Cell Proliferation; Drug Synergism; Drug Therapy, Combination; Epithelial Cells; Fatty Acids, Monounsaturated; gamma-Tocopherol; Humans; Linoleic Acid; Male; Molecular Structure; Prostate; Prostatic Neoplasms; Sphingolipids

Omega-3 (n-3) fatty acids (FA) have been proposed to confer tumor-inhibitory properties. In vivo, dietary FA are delivered to tumor cells by two main routes: low-density lipoproteins (LDL) and albumin complexes. High FA concentration in LDL and up-regulation of LDL receptors in tumor cells suggest that the LDL receptor pathway may be the major route for FA delivery. We compared effects of n-3FA delivered to human cancer cells by LDL and albumin.. LDL was isolated from plasma of African Green monkeys fed diets enriched in fish oil (n-3 FA) or linoleic acid (n-6FA) and used to deliver FA to MCF-7 and PC3 cancer cells. Cell proliferation, apoptosis, and changes in global gene expression were monitored.. Both LDL and albumin were effective in delivering FA to tumor cells and modifying the composition of cell phospholipids. The molar ratio of 20:4 (n-6) to 20:5 (n-3) in phosphatidylcholine and phosphatidylethanolamine was profoundly decreased. Although cell phospholipids were similarly modified by LDL and albumin-delivered FA, effects on cell proliferation and on transcription were markedly different. LDL-delivered n-3 FA were more effective at inhibiting cell proliferation and inducing apoptosis. Expression microarray profiling showed that a significantly higher number of genes were regulated by LDL-delivered than albumin-delivered n-3 FA with little overlap between the two sets of genes.. These results show the importance of the LDL receptor pathway in activating molecular mechanisms responsible for the tumor inhibitory properties of n-3FA.

Topics: Albumins; Animals; Apoptosis; Breast Neoplasms; Cell Proliferation; Chlorocebus aethiops; Cholesterol; Drug Delivery Systems; Fatty Acids, Omega-3; Female; Fish Oils; Gene Expression Profiling; Humans; Linoleic Acid; Lipoproteins, LDL; Male; Oligonucleotide Array Sequence Analysis; Phosphatidylcholines; Phosphatidylethanolamines; Prostatic Neoplasms; Triglycerides; Tumor Cells, Cultured

Topics: Fatty Acids, Unsaturated; Humans; Linoleic Acid; Male; Middle Aged; Prostatic Neoplasms

Topics: Case-Control Studies; Fatty Acids; Humans; Linoleic Acid; Male; Prostate; Prostatic Hyperplasia; Prostatic Neoplasms; Risk Factors

Epidemiologic and animal model studies suggest that consumption of soy isoflavones may be associated with reduced risk of prostate cancer (PC). In addition, animal model studies suggest that conjugated linoleic acid (CLA), a natural positional isomer of linoleic acid, inhibits tumor growth in various models, including models of PC.. Based on the above-mentioned data, the objective of the present study was to test the hypothesis that supplementation of the diet with combinations of isoflavone-rich soy protein isolate and CLA would act to inhibit the growth of androgen-independent R-3327-AT-1 rat prostate tumor cells inoculated ectopically into male Copenhagen rats.. The results of this study indicate that neither an isoflavone-rich soy protein isolate (SPI), nor CLA inhibit the in vivo growth and development of prostate tumor cells when administered in the diet either singly or in combination. Moreover, at the highest concentrations SPI and CLA (i.e., 20% SPI, 1% CLA), there was a statistically significant increase in tumors volume over controls. Administration of SPI at 10% in the diet also enhanced tumor growth, whereas at 5%, SPI exerted no measurable effect. CLA administration alone had no observable effects on AT-1 tumor growth.. These results, in an established rat model, suggest caution in using isoflavone-rich SPI in human studies involving advanced hormone-refractory prostate cancer until further investigation of these effects are completed.

Topics: Animals; Body Weight; Cell Division; Isoflavones; Linoleic Acid; Male; Prostatic Neoplasms; Rats; Rats, Inbred Strains; Soybean Proteins; Tumor Cells, Cultured; Xenograft Model Antitumor Assays

Topics: Adenocarcinoma; Arachidonate 15-Lipoxygenase; Arachidonic Acid; Base Sequence; Chromatography, High Pressure Liquid; DNA Primers; Humans; Linoleic Acid; Male; Prostatic Neoplasms; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Transcription, Genetic; Tumor Cells, Cultured

Dietary fatty acids may influence prostate carcinogenesis. Although the standard for assessing dietary effects in humans is the semiquantitative food-frequency questionnaire, the extent to which self-reported intake correctly ranks prostatic exposure is unknown.. The objective was to examine the correlation between reported intakes of different fatty acids and their concentrations in prostate tissue.. This was a cross-sectional study of 52 men undergoing surgical resection of the prostate gland. Usual dietary intake of saturated, total unsaturated, oleic, and linoleic fatty acids over the previous year was estimated with use of a 122-item version of the Health Habits and History Questionnaire. Concentrations in prostate tissue were measured directly by use of gas chromatography in healthy tissue collected at the time of surgery and were expressed as a percentage of total fatty acids. Correlations with 4 measures of dietary intake [g/d, g/d adjusted for total daily energy intake, % of total fat (as g/d), and % of total energy] were evaluated by Spearman's rank-order correlation coefficients.. Linoleic acid concentrations in prostate tissue were significantly correlated with dietary intake expressed as g/d adjusted for total energy [r = 0.29 (95% CI: 0.03, 0.49), P = 0.04], % of total fat [r = 0.36 (0.14, 0.550), P = 0.008], and % of total energy [r = 0.28 (0.04, 0.49), P = 0.042], but not as g/d. Although mean concentrations of saturated, total unsaturated, and oleic fatty acids in prostate tissue resembled mean intakes for the group, prostatic concentrations did not correlate with individual intakes.. Self-reported intake of fatty acids is a satisfactory marker of prostatic exposure at the group level, but, with the exception of linoleic acid, does not correctly rank individuals with respect to intensity of exposure.

Topics: Aged; Biomarkers; Chromatography, Gas; Cross-Sectional Studies; Diet; Fatty Acids; Humans; Linoleic Acid; Male; Prostate; Prostatic Neoplasms; Risk Factors; Self Disclosure; Statistics, Nonparametric; Surveys and Questionnaires

The effect of overexpression of 15-lipoxygenase-1 (15-LO-1) was studied in the human prostate cancer cell line, PC-3. Stable PC-3 cell lines were generated by transfection with 15-LO-1-sense (15-LOS), 15-LO-1-antisense (15-LOAS) or vector (Zeo) and selection with Zeocin. After characterization by RT-PCR, western and HPLC, a PC3-15LOS clone was selected that possessed 10-fold 15-LO-1 enzyme activity compared with parental PC-3 cells. The PC3-15LOAS clone displayed little or no 15-LO-1 activity. These PC-3 cell lines were characterized for properties of tumorigenesis. The proliferation rates of the cell lines were as follows: PC3-15LOS > PC-3 = PC3-Zeo > PC3-15LOAS. Addition of a specific 15-LO-1 inhibitor, PD146176, caused a dose-dependent inhibition of proliferation in vitro. Overexpression of 15-LO-1 also caused [(3)H]thymidine incorporation to increase by 4.0-fold (P < 0.01). Compared with parental and PC-3-Zeo cells, PC3-15LOS enhanced whereas PC3-15LOAS reduced the ability of PC-3 cells to grow in an anchorage-independent manner, as assessed by colony formation in soft agar. These data suggested a pro-tumorigenic role for 15-LO-1 in PC-3 cells in vitro. Therefore, to clarify the role of 15-LO-1 in vivo, the effect of 15-LO-1 expression on the growth of tumors in nude mice was investigated. The PC-3 cell lines were inoculated subcutaneously into athymic nude mice. The frequency of tumor formation was increased and the sizes of the tumors formed were much larger in the PC3-15LOS compared with PC3-15LOAS, parental PC-3 and PC-3-Zeo cells. Immunohistochemistry for 15-LO-1 confirmed expression throughout the duration of the experiment. The expression of factor VIII, an angiogenesis marker, in tumor sections was increased in tumors derived from PC3-15LOS cells and decreased in those from PC3-15LOAS cells compared with tumors from parental or Zeo cells. These data further supported the evaluation by ELISA of vascular endothelial growth factor (VEGF) secretion by PC-3 cells in culture. Secretion of this angiogenic factor was elevated in PC3-15LOS cells compared with the other cell lines. These results support a role for 15-LO-1 in a novel growth-promoting pathway in the prostate.

Topics: Adenocarcinoma; Animals; Arachidonate 15-Lipoxygenase; Blotting, Western; Cell Division; Chromatography, High Pressure Liquid; Colony-Forming Units Assay; Electrophoresis, Polyacrylamide Gel; Endothelial Growth Factors; Enzyme Induction; Factor VIII; Humans; Immunoenzyme Techniques; Linoleic Acid; Linoleic Acids; Lymphokines; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Prostatic Neoplasms; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Transfection; Tumor Cells, Cultured; Tumor Suppressor Protein p53; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors

We recently reported that the mutant form of the tumor-suppressor gene p53 up-regulates 15-LO-1 gene expression in a murine cell line. Here, we examine the expression of 15-lipoxygenase (LO)-1 and mutant p53 (mtp53) in human prostatic tissues and 15-LO-1 in the human prostate adenocarcinoma cell line PC-3. Reverse transcription-PCR and western analyses conclusively demonstrated expression of 15-LO-1 in PC-3 cells. Western blotting for 15-LO-1 in freshly resected 'normal' and prostate adenocarcinoma specimens showed 15-LO-1 expression in normal tissue, but significantly higher levels were detected in prostate adenocarcinomas. Prostate adenocarcinoma tissues generated chirally pure 13-S-hydroxyoctadecadienoic acid from exogenous linoleic acid, a preferred substrate of 15-LO-1. To study the correlation of 15-LO-1 expression with mtp53 in prostate cancer, we immunostained 48 prostatectomy specimens obtained by transurethral resection of the prostate and needle biopsy (median age 68 years, range 52-93) of different Gleason grades (n = 48), using antibodies specific for 15-LO-1, mtp53 and MIB-1 (a proliferation marker). We compared staining in cancerous foci with adjacent normal appearing prostate tissues. In only 5 of 48 patients did 'normal' tissue adjacent to cancerous foci display staining for 15-LO-1. However, no staining for mtp53 was observed in any of the normal tissues. In cancer foci, robust staining was observed for both 15-LO-1 (36 of 48, 75%) and mtp53 (19 of 48, 39%). Furthermore, the intensities of expression of 15-LO-1 and mtp53 correlated positively with each other (P < 0.001) and with the degree of malignancy, as assessed by Gleason grading (P < 0.01). By immunohistochemistry, 15-LO-1 was located in secretory cells of peripheral zone glands, prostatic ducts and seminal vesicles, but not in the basal cell layer or stroma. Based on these and other studies, we propose a model describing a possible role for 15-LO-1 expression in influencing the malignant potential and pathobiological behavior of adenocarcinomas.

Topics: Adenocarcinoma; Arachidonate 15-Lipoxygenase; Arachidonic Acid; Blotting, Western; Enzyme Induction; Humans; Immunohistochemistry; Linoleic Acid; Linoleic Acids; Male; Mutation; Neoplasm Staging; Prostatic Neoplasms; Reverse Transcriptase Polymerase Chain Reaction; Stereoisomerism; Tumor Cells, Cultured; Tumor Suppressor Protein p53

Topics: Breast Neoplasms; Colonic Neoplasms; Dietary Fats, Unsaturated; Female; Humans; Linoleic Acid; Male; Prostatic Neoplasms

Polyunsaturated fatty acids (n-6) are reported to selectively kill malignant cells. Most investigations, however, did not compare neoplastic with non-neoplastic cells from the same tissue type. Here we evaluate the effects of n-6 fatty acids on a non-neoplastic epithelium cell line (CAPE) and a spontaneous carcinoma cell line (CPA) derived from the canine prostate.. Cell lines were cultured in DME in the presence of fatty acids and their effects on cell proliferation monitored by coulter counting. Lipids were extracted and quantitized by gas chromatography.. Cell proliferation was reduced more in CAPE. A neoplastic strain (CPA-GLA) tolerant to prolonged culture in 18:3n-6 was isolated. CPA grown in an 18:2n-6 or 18:3n-6 supplemented media accumulated 20:3n-6 and contained little 20:4n-6.. Polyenoic n-6 fatty acids are not specifically inhibitory to neoplastic cells which exhibited a marked alteration in the metabolism of 20:4n-6.

Topics: Animals; Arachidonic Acid; Cell Division; Cells, Cultured; Dogs; gamma-Linolenic Acid; Linoleic Acid; Linoleic Acids; Lipids; Male; Prostate; Prostatic Neoplasms; Tumor Cells, Cultured

Ecological and case-control studies have demonstrated a positive correlation between consumption of fat and the risk of prostate cancer. Two recent human studies have focused on alpha-linolenic acid as a risk factor for prostate cancer. Animal experiments have shown that dietary omega-6 polyunsaturated fatty acids have generally stimulated tumour development, whereas omega-3 polyunsaturated fatty acids have diminished it. The aim of our study was to investigate the association between these fatty acids and the subsequent risk of prostate cancer. Blood donors to the Janus serum data bank in Norway, who later developed prostate cancer, were matched to blood donors without prostate cancer (141 matched sets); the proportional level of fatty acids measured before diagnosis in the donors' serum was examined. The risk of later prostate cancer was analysed by conditional logistic regression. Increasing risk for prostate cancer was found with increasing quartiles of palmitoleic, palmitic and alpha-linolenic acid. An inverse risk association was found with increasing levels of tetracosanoic acid, for the ratios of linoleic to alpha-linolenic acid and arachidonic to eicosapentaenoic acid. There was no clear association between the risk effect of total omega-3 and total omega-6 fatty acids. There were no indications of a relationship between fatty acids and more aggressive cancers. Our results verify recent findings of a positive association between alpha-linolenic acid and a negative association between the ratio of linoleic to alpha-linolenic acid and the risk of prostate cancer.

Topics: alpha-Linolenic Acid; Case-Control Studies; Dietary Fats; Fatty Acids; Fatty Acids, Omega-3; Fatty Acids, Omega-6; Fatty Acids, Unsaturated; Humans; Incidence; Linoleic Acid; Linoleic Acids; Male; Middle Aged; Norway; Phospholipids; Prostatic Neoplasms; Risk Factors; Single-Blind Method

Animal and ecological studies suggest that linoleic acid intake is related to breast-cancer incidence. Analytical epidemiologic studies, however, do not support such findings. The primary objective of our ecological study was to investigate the association between breast-cancer incidence and linoleic acid status across European countries. In addition, other fatty acids and cancer sites were studied. Mean fatty acid composition of adipose tissue samples in 11 centres from 8 European countries and Israel served as indicators of exposure of the population. Figures on cancer incidence for the respective or comparable regions were obtained from published data. N-6 fatty acids in adipose tissue ranged from 10.4 in Helsinki to 24.6 g/100 g fatty acids in Jerusalem. N-6 fatty acids were not associated significantly with breast, colon or prostate cancer. Cancers of the breast and colon were associated negatively with cis-mono-unsaturated fatty acids and positively with trans fatty acids. Despite a large range in intake, we found no evidence of a positive association between n-6 fatty acid status and breast cancer, but associations were observed between other fatty acids and cancer. Differences in linoleic acid intake cannot explain risk differences in breast-cancer incidence between affluent countries, while associations of other fatty acids with cancer rates may reflect cultural differences.

Topics: Adipose Tissue; Aged; Biomarkers, Tumor; Breast Neoplasms; Case-Control Studies; Colonic Neoplasms; Europe; Fatty Acids; Fatty Acids, Omega-3; Fatty Acids, Omega-6; Fatty Acids, Unsaturated; Female; Humans; International Cooperation; Israel; Linoleic Acid; Linoleic Acids; Male; Middle Aged; Prostatic Neoplasms; Risk Factors

Animal studies have suggested that omega-6 fatty acids found in vegetable oils may promote prostate cancer. Our goal was to use erythrocyte membrane and adipose tissue fatty acid composition as biomarkers to investigate whether essential fatty acids modulated prostate cancer risk. An outpatient clinic-based study of 89 cases and 38 controls was conducted in North Carolina between July 1989 and December 1991. Cases were recruited from a university-based urology outpatient clinic. Eligible cases were more than 45 years of age and had histological confirmation of a prostate cancer diagnosis within 1 year of entry into the study. Controls were histologically confirmed free of prostate cancer. Erythrocyte membranes from venous blood and adipose tissue fatty acids from s.c. fat samples were analyzed in batches using capillary gas chromatography. Unconditional logistic regression analysis was used to calculate odds ratios for the association of each fatty acid with prostate cancer while controlling for potential confounders. Linoleic acid consumption was positively associated with prostate cancer risk. The odds ratios comparing the first and fourth quartiles of linoleic acid consumption were 3.54 (95% confidence interval, 1.0-12.53) with P trend < 0.04 for erythrocyte membranes, and 2.47 (95% confidence interval, 0.66-9.26) with P trend < 0.08 for adipose tissue. These data suggest that linoleic acid consumption may increase prostate cancer risk, which is consistent with results from animal experiments. Linoleic acid is found in vegetable oils used in cooking and in cereals, snack foods, and baked goods. Our data failed to demonstrate consistently a protective effect of marine omega-3 fatty acids on prostate cancer.

Topics: Adipose Tissue; Aged; Biomarkers; Chromatography, Gas; Dietary Fats, Unsaturated; Erythrocyte Membrane; Fatty Acids, Essential; Fatty Acids, Omega-3; Fatty Acids, Omega-6; Fatty Acids, Unsaturated; Humans; Linoleic Acid; Linoleic Acids; Logistic Models; Male; Middle Aged; Prostatic Neoplasms; Risk Factors

Human prostate cancer (PC) cell lines possess epidermal growth factor (EGF) receptors and secrete EGF-related polypeptides. We used an EGF receptor-blocking antibody (anti-EGF.R) to demonstrate a functional autocrine loop, as well as the interaction between this and the effects of linoleic acid (LA), an omega-6 fatty acid, on PC cell growth. The anti-EGF.R competed effectively with [125I]EGF for receptors on DU145 PC cells, and on a high-passage DU145 variant (DU145M); when added to the culture medium, it suppressed both DU145 and DU145M cell growth in a dose-dependent manner. LA, a precursor for eicosanoid synthesis, had little effect on DU145 cell growth rate but stimulated DU145M growth in a concentration-related manner over a range of 0.25-2.0 micrograms/ml. anti-EGF.R (10(-9) M) caused suppression of LA-stimulated growth of DU145M cells in serum-free medium, which was prevented by the addition of 2 nM EGF. We conclude that an EGF.R-mediated autocrine loop is involved in PC cell growth regulation and that at least one site of action may be the synthesis of eicosanoids from their LA precursor.

Topics: Binding, Competitive; Cell Division; Epidermal Growth Factor; ErbB Receptors; Humans; Linoleic Acid; Linoleic Acids; Male; Prostatic Neoplasms; Tumor Cells, Cultured

Dietary fatty acids (FAs) may be involved in the carcinogenic process within the prostate gland and progression to clinically manifest disease. We have shown that growth of the androgen-unresponsive PC-3 human prostate cancer cell line is stimulated in vitro by the presence of linoleic acid (LA), an omega-6 polyunsaturated FA. The response was positively related to the FA concentration over the entire range examined (5-750 ng/ml). Conversely, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), two omega-3 FAs present in fish oils, inhibited PC-3 cell growth in a dose-dependent manner; both were equally effective, with an approximately 65% reduction in growth occurring at a concentration of 2.0 micrograms/ml (P less than 0.001). The DU 145 human prostate cancer cell line, which is also androgen-unresponsive, showed no growth response to LA and was less susceptible to growth inhibition when cultured in the presence of omega-3 FAs. Growth experiments with indomethacin, esculetin, and piroxicam, pharmacological inhibitors of eicosanoid biosynthesis with differing sites of action, indicated that human prostate cancer cell growth requires intact metabolic pathways for both leukotriene and prostaglandin production.

Topics: Cell Division; Eicosanoids; Fatty Acids; Humans; Indomethacin; Linoleic Acid; Linoleic Acids; Male; Piroxicam; Prostatic Neoplasms; Tumor Cells, Cultured; Umbelliferones

Linoleic acid, an omega-6 unsaturated fatty acid, stimulated growth of the MDA-MB-231 and MCF-7 human breast cancer cell lines in culture. Responses of the estrogen-independent MDA-MB-231 cells both in serum-free medium and with 1% fetal bovine serum added were positively correlated with linoleic acid concentration over the entire range examined (5-750 ng/ml). Growth stimulation of the estrogen-responsive MCF-7 cell line was maximal at a LA concentration of 500 ng/ml when cultured in 1% fetal bovine serum-containing medium with added estradiol. Linoleic acid had no mitogenic effect on three human cancer cell lines derived from sites other than breast, or on untransformed 3T3 cells.

Topics: Breast Neoplasms; Carcinogens; Dietary Fats; Humans; Linoleic Acid; Linoleic Acids; Lung Neoplasms; Male; Prostatic Neoplasms; Skin Neoplasms; Tumor Cells, Cultured