coenzyme-q10 and Neoplasms

Coenzyme Q

Topics: Biological Availability; Dietary Supplements; Humans; Migraine Disorders; Neoplasms; Neurodegenerative Diseases; Neuromuscular Diseases; Quality of Life; Ubiquinone

Dihydroorotate dehydrogenase (DHODH) is an enzyme of the de novo pyrimidine synthesis pathway that provides nucleotides for RNA/DNA synthesis essential for proliferation. In mammalian cells, DHODH is localized in mitochondria, linked to the respiratory chain via the coenzyme Q pool. Here we discuss the role of DHODH in the oxidative phosphorylation system and in the initiation and progression of cancer. We summarize recent findings on DHODH biology, the progress made in the development of new, specific inhibitors of DHODH intended for cancer therapy, and the mechanistic insights into the consequences of DHODH inhibition.

Topics: Cell Proliferation; Dihydroorotate Dehydrogenase; Electron Transport; Enzyme Inhibitors; Humans; Mitochondria; Neoplasms; Oxidative Phosphorylation; Oxidoreductases Acting on CH-CH Group Donors; Ubiquinone

Coenzyme Q-10 (CoQ10) is a widely used alternative medication or dietary supplement and one of its roles is as an antioxidant. It naturally functions as a coenzyme and component of oxidative phosphorylation in mitochondria. Decreased levels have been demonstrated in diseased myocardium and in Parkinson disease. Farnesyl pyrophosphate is a critical intermediate for CoQ10 synthesis and blockage of this step may be important in statin myopathy. Deficiency of CoQ10 also has been associated with encephalomyopathy, severe infantile multisystemic disease, cerebellar ataxia, nephrotic syndrome, and isolated myopathy. Although supplementation with CoQ10 has been reported to be beneficial in treating hypertension, congestive heart failure, statin myopathy, and problems associated with chemotherapy for cancer treatement, this use of CoQ10 as a supplement has not been confirmed in randomized controlled clinical trials. Nevertheless, it appears to be a safe supplementary medication where usage in selected clinical situations may not be inappropriate. This review is an attempt to actualize the available information on CoQ10 and define its potential benefit and appropriate usage.

Topics: Animals; Cardiovascular Diseases; Heart Failure; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypertension; Muscular Diseases; Neoplasms; Ubiquinone

The oxidative pentose phosphate pathway (PPP) contributes to tumour growth, but the precise contribution of 6-phosphogluconate dehydrogenase (6PGD), the third enzyme in this pathway, to tumorigenesis remains unclear. We found that suppression of 6PGD decreased lipogenesis and RNA biosynthesis and elevated ROS levels in cancer cells, attenuating cell proliferation and tumour growth. 6PGD-mediated production of ribulose-5-phosphate (Ru-5-P) inhibits AMPK activation by disrupting the active LKB1 complex, thereby activating acetyl-CoA carboxylase 1 and lipogenesis. Ru-5-P and NADPH are thought to be precursors in RNA biosynthesis and lipogenesis, respectively; thus, our findings provide an additional link between the oxidative PPP and lipogenesis through Ru-5-P-dependent inhibition of LKB1-AMPK signalling. Moreover, we identified and developed 6PGD inhibitors, physcion and its derivative S3, that effectively inhibited 6PGD, cancer cell proliferation and tumour growth in nude mice xenografts without obvious toxicity, suggesting that 6PGD could be an anticancer target.

Topics: AMP-Activated Protein Kinase Kinases; AMP-Activated Protein Kinases; Humans; Lipogenesis; Neoplasms; Oxidative Stress; Pentose Phosphate Pathway; Phosphogluconate Dehydrogenase; Protein Serine-Threonine Kinases; Ribulosephosphates; Signal Transduction

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 promising theoretical possibilities of antioxidant prevention and protection against vascular diseases and neoplasms could not have been realized as yet. The author searches into the causes of this failure by analyzing data of recent literature. Previous preventive trials as well as newly discovered pharmacological and molecular biological effects of antioxidants are reviewed. Results of meta-analyses on prevention trials of vascular disease by vitamin-E and those of gastrointestinal cancers are also included. The lately recognized properties of antioxidants are surveyed with special regard to their capability of modulating apoptosis, inducing gene expressions and their transformation into pro-oxidants. The harmful consequence of high doses of a single antioxidant is emphasized. The retinoids, vitamins D and K possess both pro-apoptotic and antiproliferative activity, while N-acetylcysteine exerts mainly anti-apoptotic effects. Since the effects of the eight vitamin E homologues are different in many respects, alpha-tocopherol can not be regarded as vitamin E of full value. Antioxidant supply from natural sources does not seem to be sufficient for an adequate preventive effect. The author recommends such a combination in which physiological amounts of vitamins C, D, K and B-complex, N-acetylcysteine, vitamin E of natural origin might be complemented by allopurinol, co-enzyme Q-10 and alpha-lipoic acid. A diet rich in flavonoids and carotenoids is essential. Application of appropriate laboratory methods is of great value in the individualization, monitoring and control of antioxidant treatment.

Topics: Acetylcysteine; Allopurinol; Antioxidants; Apoptosis; Ascorbic Acid; Cardiovascular Diseases; Clinical Trials as Topic; Coenzymes; Flavonoids; Humans; Meta-Analysis as Topic; Neoplasms; Selenium; Ubiquinone; Vitamin A; Vitamin D; Vitamin E; Vitamin K; Vitamins

Preclinical and clinical studies suggest that anthracycline-induced cardiotoxicity can be prevented by administering coenzyme Q10 during cancer chemotherapy that includes drugs such as doxorubicin and daunorubicin. Studies further suggest that coenzyme Q10 does not interfere with the antineoplastic action of anthracyclines and might even enhance their anticancer effects. Preventing cardiotoxicity might allow for escalation of the anthracycline dose, which would further enhance the anticancer effects. Based on clinical investigation, although limited, a cumulative dose of doxorubicin of up to 900 mg/m2, and possibly higher, can be administered safely during chemotherapy as long as coenzyme Q10 is administered concurrently. The etiology of the dose-limiting cardiomyopathy that is induced by anthracyclines can be explained by irreversible damage to heart cell mitochondria, which differ from mitochondria of other cells in that they possess a unique enzyme on the inner mitochondrial membrane. This enzyme reduces anthracyclines to their semiquinones, resulting in severe oxidative stress, disruption of mitochondrial energetics, and irreversible damage to mitochondrial DNA. Damage to mitochondrial DNA blocks the regenerative capability of the organelle and ultimately leads to apoptosis or necrosis of myocytes. Coenzyme Q10, an essential component of the electron transport system and a potent intracellular antioxidant, appears to prevent damage to the mitochondria of the heart, thus preventing the development of anthracycline-induced cardiomyopathy.

Topics: Animals; Anthracyclines; Antibiotics, Antineoplastic; Antioxidants; Cardiomyopathies; Coenzymes; Cytoprotection; Dose-Response Relationship, Drug; Drug Therapy, Combination; Heart; Heart Failure; Humans; Mitochondria, Heart; Neoplasms; Ubiquinone

Coenzyme Q10 (ubiquinone) is a naturally occurring compound widely distributed in animal organisms and in humans. The primary compounds involved in the biosynthesis of ubiquinone are 4-hydroxybenzoate and the polyprenyl chain. An essential role of coenzyme Q10 is as an electron carrier in the mitochondrial respiratory chain. Moreover, coenzyme Q10 is one of the most important lipophilic antioxidants, preventing the generation of free radicals as well as oxidative modifications of proteins, lipids, and DNA, it and can also regenerate the other powerful lipophilic antioxidant, alpha-tocopherol. Antioxidant action is a property of the reduced form of coenzyme Q10, ubiquinol (CoQ10H2), and the ubisemiquinone radical (CoQ10H*). Paradoxically, independently of the known antioxidant properties of coenzyme Q10, the ubisemiquinone radical anion (CoQ10-) possesses prooxidative properties. Decreased levels of coenzyme Q10 in humans are observed in many pathologies (e.g. cardiac disorders, neurodegenerative diseases, AIDS, cancer) associated with intensive generation of free radicals and their action on cells and tissues. In these cases, treatment involves pharmaceutical supplementation or increased consumption of coenzyme Q10 with meals as well as treatment with suitable chemical compounds (i.e. folic acid or B-group vitamins) which significantly increase ubiquinone biosynthesis in the organism. Estimation of coenzyme Q10 deficiency and efficiency of its supplementation requires a determination of ubiquinone levels in the organism. Therefore, highly selective and sensitive methods must be applied, such as HPLC with UV or coulometric detection.

Topics: Animals; Antioxidants; Coenzymes; Cytoprotection; Free Radicals; Humans; Mitochondria; Neoplasms; Neurodegenerative Diseases; Ubiquinone

The aim of this systematic review was to summarize and evaluate the evidence available for oral supplementation with coenzyme Q10 (CoQ10) to improve the tolerability of cancer treatments.. Searches for all published and unpublished controlled trials were carried out on seven databases. Manufacturers of CoQ10 were identified and contacted. Controlled clinical trials of monopreparations of CoQ10 administered orally to cancer patients were included. No language restrictions were imposed. Data were extracted independently by two authors according to predefined criteria.. Six studies were included in the review, including three randomized clinical trials and three nonrandomized clinical trials. Patients in five of six studies received anthracyclines. The results suggested that CoQ10 provides some protection against cardiotoxicity or liver toxicity during cancer treatment. However, because of inadequate reporting and analysis, as well as questionable validity of outcome measures, the results are not conclusive.. Suggestions that CoQ10 might reduce the toxicity of cancer treatments have not been tested by rigorous trials. Further investigations are necessary to determine whether CoQ10 can improve the tolerability of cancer treatments.

Topics: Antineoplastic Agents; Antioxidants; Coenzymes; Controlled Clinical Trials as Topic; Cytoprotection; Humans; Neoplasms; Ubiquinone

ECTO-NOX (because of their cell surface location) proteins comprise a family of NAD(P)H oxidases of plants and animals that exhibit both oxidative and protein disulfide isomerase-like activities. The two biochemical activities, hydroquinone [NAD(P)H] oxidation and protein disulfide--thiol interchange alternate, a property unprecedented in the biochemical literature. A tumor-associated ECTO-NOX (tNOX) is cancer-specific and drug-responsive. The constitutive ECTO-NOX (CNOX) is ubiquitous and refractory to drugs. The physiological substrate for the oxidative activity appears to be hydroquinones of the plasma membrane such as reduced coenzyme Q10. ECTO-NOX proteins are growth-related and drive cell enlargement. Also indicated are roles in aging and in neurodegenerative diseases. The regular pattern of oscillations appears to be related to alpha-helix-beta-structure transitions and serves biochemical core oscillator of the cellular biological clock. Period length is independent of temperature (temperature compensated) and synchrony is achieved through entrainment.

Topics: Aging; Amino Acid Motifs; Amino Acid Sequence; Animals; Biological Clocks; Cell Division; Cell Membrane; Coenzymes; Humans; Models, Biological; Molecular Sequence Data; Multienzyme Complexes; NADH, NADPH Oxidoreductases; Neoplasms; Neurodegenerative Diseases; Oxygen; Prions; Sequence Homology, Amino Acid; Temperature; Time Factors; Ubiquinone

Topics: Antioxidants; Ascorbic Acid; Coenzymes; Humans; Neoplasms; Ubiquinone; Vitamin E

Randomized controlled trials are generally regarded as the gold standard of study designs to determine causality. The inclusion of a placebo group in these trials, when appropriate, is critical to access the efficacy of a drug or supplement. The placebo response itself has received some attention in the medical literature over the past fifty years. The recent increasing utilization of dietary supplements and herbal medications by patients makes it imperative to reevaluate the placebo response in conventional and alternative medicine. This article will review some of the negative and positive results from randomized trials utilizing dietary supplements (androstenedione, beta-carotene, CoQ10, garlic, soy, vitamin C and E...) for a number of non-urologic and urologic conditions, including cancer.

Topics: Androstenedione; Antioxidants; beta Carotene; Coenzymes; Complementary Therapies; Dehydroepiandrosterone; Garlic; Heart Failure; Hot Flashes; Humans; Libido; Neoplasms; Placebo Effect; Randomized Controlled Trials as Topic; Ubiquinone; Vitamin E

Coenzyme Q10 or ubiquinone has been shown to have both anti-cancer and immune system enhancing properties when tested in animals. Preliminary results reported here suggest that it might inhibit tumour-associated cytokines. Clinical studies conducted with combination therapies of CoQ10 and other antioxidants are ongoing, but the results are difficult evaluate owing to the lack of proper control groups and of initial randomisation. Also on the basis of some anti-cancer effects of antioxidants reported in literature, further animal studies and a proper clinical trial of coenzyme Q10 in cancer patients are needed.

Topics: Animals; Anticarcinogenic Agents; Antineoplastic Agents; Antioxidants; Clinical Trials as Topic; Coenzymes; Cytokines; Humans; Neoplasms; Ubiquinone

New data on blood levels of vitamin Q10 in 116 cancer patients reveal an incidence of 23.1% of patients (N=17) with breast cancer whose blood levels were below 0.5 microg/ml. The incidence of breast cancer cases with levels below 0.6 microg/ml was 38.5%. The incidence is higher (p<0.05) than that for a group of ordinary people. Patients (N=15) with myeloma showed a mean blood level of 0.67 +/- 0.17 microg/ml. The incidence of a vitamin Q10 blood level below 0.7 microg/ml for these 15 cases of myeloma was 53.3%, which is higher (p<0.05) than the 24.5% found for a group of ordinary people.

Topics: Animals; Breast Neoplasms; Coenzymes; Female; Humans; Male; Multiple Myeloma; Neoplasms; Neoplasms, Experimental; Reference Values; Ubiquinone

Over ca. 25 years, assays in animal models established the hematopoietic activities of coenzyme Q's in rhesus monkeys, rabbits, poultry, and children having kwashiorkor. Surprisingly, a virus was found to cause a deficiency of CoQ9. Patients with AIDS showed a-"striking"-clinical response to therapy with CoQ10. The macrophage potentiating activity of CoQ10 was recorded by the carbon clearance method. CoQ10 significantly increased the levels of IgG in patients. Eight new case histories of cancer patients plus two reported cases support the statement that therapy of cancer patients with CoQ10, which has no significant side effect, has allowed survival on an exploratory basis for periods of 5-15 years. These results now justify systematic protocols.

Topics: Aged; Animals; Bone Marrow; Coenzymes; Female; Humans; Male; Middle Aged; Neoplasms; Survival Analysis; Ubiquinone

Topics: Animals; Emulsions; G(M1) Ganglioside; Immunotherapy; Mice; N-Acetylneuraminic Acid; Neoplasms; Selectins; Ubiquinone

Oncogene activation and loss of tumor suppressor function changes the metabolic activity of cancer cells to drive unrestricted proliferation. Moreover, cancer cells adapt their metabolism to sustain growth and survival when access to oxygen and nutrients is restricted, such as in poorly vascularized tumor areas. We show here that p53-deficient colon cancer cells exposed to tumor-like metabolic stress in spheroid culture activated the mevalonate pathway to promote the synthesis of ubiquinone. This was essential to maintain mitochondrial electron transport for respiration and pyrimidine synthesis in metabolically compromised environments. Induction of mevalonate pathway enzyme expression in the absence of p53 was mediated by accumulation and stabilization of mature SREBP2. Mevalonate pathway inhibition by statins blocked pyrimidine nucleotide biosynthesis and induced oxidative stress and apoptosis in p53-deficient cancer cells in spheroid culture. Moreover, ubiquinone produced by the mevalonate pathway was essential for the growth of p53-deficient tumor organoids. In contrast, inhibition of intestinal hyperproliferation by statins in an Apc/KrasG12D-mutant mouse model was independent of

Topics: Animals; Apoptosis; Cell Line, Tumor; Cell Survival; Citric Acid Cycle; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Intestinal Mucosa; Mevalonic Acid; Mice; Mice, Transgenic; Neoplasms; Pyrimidines; Signal Transduction; Sterol Regulatory Element Binding Protein 2; Stress, Physiological; Tumor Microenvironment; Tumor Suppressor Protein p53; Ubiquinone; Xenograft Model Antitumor Assays

Topics: Animals; Antineoplastic Agents; Antioxidants; Cisplatin; Coenzymes; Doxorubicin; Drug Interactions; Glutathione; Humans; Neoplasms; Oxidative Stress; Reactive Oxygen Species; Treatment Outcome; Ubiquinone

The objective of this study was to test the hypothesis that doxorubicin treatment for cancer in childhood and adolescence causes a dose-related decrease in the concentration of plasma coenzyme Q(10). The concentration of plasma coenzyme Q(10) was measured before and after administration of doxorubicin in six patients, and before and after chemotherapy in six patients undergoing treatments that did not include doxorubicin. There was a significant increase in the concentration of plasma coenzyme Q(10) in post-treatment samples compared to pre-treatment samples in patients treated with doxorubicin (P=0.008; n=32), whereas there were no significant changes in plasma coenzyme Q(10) concentrations in patients treated with chemotherapy that did not include doxorubicin. (P=0.770; n=30). We hypothesise that the increase in plasma coenzyme Q(10) that was observed in patients undergoing doxorubicin treatment is due to release of coenzyme Q(10) from apoptotic or necrotic cardiac tissue. We conclude that the cardiotoxicity due to doxorubicin therapy does not involve acute myocardial depletion of coenzyme Q(10).

Topics: Adolescent; Adult; Antineoplastic Agents; Antioxidants; Child; Child, Preschool; Cholesterol; Coenzymes; Cytoprotection; Doxorubicin; Female; Heart Diseases; Humans; Male; Neoplasms; Ubiquinone

In the human, coenzyme Q10 (vitamin Q10) is biosynthesized from tyrosine through a cascade of eight aromatic precursors. These precursors indispensably require eight vitamins, which are tetrahydrobiopterin, vitamins B6, C, B2, B12, folic acid, niacin, and pantothenic acid as their coenzymes. Three of these eight vitamins (the coenzyme B6, and the coenzymes niacin and folic acid) are indispensable in the biosynthesis of the four bases (thymidine, guanine, adenine, and cytosine) of DNA. One or more of the three vitamins required for DNA are known to cause abnormal pairing of the four bases, which can then result in mutations and the diversity of cancer. The coenzyme B6, required for the conversion of tyrosine to p-hydroxybenzoic acid, is the first coenzyme required in the cascade of precursors. A deficiency of the coenzyme B6 can cause dysfunctions, prior to the formation of vitamin Q10, to DNA. Former data on blood levels of Q10 and new data herein on blood levels of B6, measured as EDTA, in cancer patients established deficiencies of Q10 and B6 in cancer. This complete biochemistry relating to biosyntheses of Q10 and the DNA bases is a rationale for the therapy of cancer with Q10 and other entities in this biochemistry.

Topics: Breast Neoplasms; Coenzymes; DNA; Female; Humans; Incidence; Neoplasms; Purines; Pyrimidines; Reference Values; Sweden; Ubiquinone; Vitamins

Topics: Coenzymes; Free Radicals; Humans; Neoplasms; Ubiquinone

Serum levels of coenzyme Q10 (CoQ10) as well as lipids were determined in patients during total parenteral nutrition (TPN). The mean CoQ10 levels (M +/- SD) were 0.77 +/- 0.30 microgram/ml for 108 normal subjects and 0.59 +/- 0.35 microgram/ml for 95 patients before TPN. The mean CoQ10 level of the patients decreased significantly to 0.35 +/- 0.23 microgram/ml one week after the start of TPN, and then remained almost unchanged during TPN for up to 6 weeks. When the patients receiving TPN (TPN patients) were grouped according to their clinical diagnoses, the mean CoQ10 level of patients with cancer was significantly lower than that of the other patients without cancer in 4 week therapy, but there was no difference in the levels between the patients with and without diseases of the gastrointestinal tract. Serum levels of total cholesterol (T-Chol) and esterified cholesterol in TPN patients also declined below their respective normal ranges, but not to the same extent in comparison to CoQ10. The levels of triglycerides (TG), phospholipids (PL), non-esterified fatty acids, low density lipoproteins, very low density lipoproteins, chylomicrons, and cholesterol in the high density lipoprotein fraction in serum of TPN patients were within their normal ranges. The levels of CoQ10 in TPN patients were correlative to those of T-Chol, TG, and PL, and decreased rapidly prior to the latter levels.

Topics: Adolescent; Adult; Aged; Cholesterol; Coenzymes; Female; Health Status; Humans; Lipids; Male; Middle Aged; Neoplasms; Parenteral Nutrition, Total; Ubiquinone

Cardiotoxicity induced by adriamycin and protective effect by coenzyme Q10 were studied in 80 closely-followed patients receiving chemotherapy with adriamycin. Serial electrocardiograms were recorded immediately before and after the administration of adriamycin each times. The electrocardiographic parameters (heart rate, P-Q duration, QRS-duration, QRS voltage and QTc-duration) were analyzed. In patients treated with adriamycin alone, QTc-duration was prolonged significantly. On the other hand, in patients treated with adriamycin plus coenzyme Q10, QTc-duration was not significantly prolonged. This Suggests that coenzyme Q10 may reduce negative inotropic action induced by adriamycin. Further, the QRS voltage was also significantly decreased in patients treated with adriamycin alone, but was not decreased in patients treated with adriamycin plus coenzyme Q10. These findings suggest that some electrocardiographic changes due to adriamycin may be prevented by coenzyme Q10.

Topics: Coenzymes; Doxorubicin; Electrocardiography; Female; Gastrointestinal Neoplasms; Heart; Heart Rate; Humans; Leukemia; Lung Neoplasms; Lymphoma; Male; Middle Aged; Neoplasms; Time Factors; Ubiquinone

Topics: Adult; Aged; Coenzymes; Female; Humans; Immunoglobulin G; Male; Middle Aged; Neoplasms; Ubiquinone

An unique combination treatment for cancer patients has been attempted in our department. The treatment consists of 500 rad irradiation of cobalt 60 on the first day and drip infusion of mixture of 50mg adriamycin, 500mg cyclophosphamide and 500mg 5-fluorouracil on the next day. This combination therapy was repeated every 3 weeks. The myocardial intoxication may be a great problem in this therapy. Investigation was performed in 40 cancer patients in order to clarify of Coenzyme Q10 (CoQ10) could show any protecting effect upon the possible myocardial intoxication. All patients were divided into 2 groups; one with CoQ10 of 20 patients, who received CoQ10 of 90mg/day orally and the other without CoQ10 of 20 patients. In the group without CoQ10, cardiothoracic ratio (CTR) and pulse rate increased significantly in all patients and on ECG low voltage of QRS complex was seen in 2 cases, changes of ST-segment, T-wave and appearance of arrhythmia were more than frequent in the group without CoQ10 than that with CoQ10. It is concluded that CoQ10 is effective for protecting the myocardium in this cancer therapy.

Topics: Adult; Aged; Breast Neoplasms; Coenzymes; Cyclophosphamide; Doxorubicin; Drug Therapy, Combination; Electrocardiography; Female; Fluorouracil; Heart; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasms; Thyroid Neoplasms; Ubiquinone