Coenzyme Q10 was first isolated in 1957, and its chemical structure (benzoquinone compound) was determined in 1958.[1,2] Interest in coenzyme Q10 as a therapeutic agent in cancer began in 1961, when a deficiency was noted in the blood of both Swedish and American cancer patients, especially in the blood of patients with breast cancer.[2,3,4] A subsequent study showed a statistically significant relationship between the level of plasma coenzyme Q10 deficiency and breast cancer prognosis. Low blood levels of this compound have been reported in patients with malignancies other than breast cancer, including myeloma, lymphoma, and cancers of the lung, prostate, pancreas, colon, kidney, and head and neck.[2,6,7] Furthermore, decreased levels of coenzyme Q10 have been detected in malignant human tissue,[8,9,10,11,12] but increased levels have been reported as well.
A large amount of laboratory and animal data on coenzyme Q10 have accumulated since 1962. Research into cellular energy-producing mechanisms that involve this compound was awarded the Nobel Prize in Chemistry in 1978. Some of the accumulated data show that coenzyme Q10 stimulates animal immune systems, leading to higher antibody levels, greater numbers and/or activities of macrophages and T cells (T lymphocytes),[13,14] and increased resistance to infection.[15,16,17] Coenzyme Q10 has also been reported to increase IgG (immunoglobulin G) antibody levels and to increase the CD4 to CD8 T-cell ratio in humans.[18,19,20] CD4 and CD8 are proteins found on the surface of T cells, with CD4 and CD8 identifying helper T cells and cytotoxic T cells, respectively; decreased CD4 to CD8 T-cell ratios have been reported for cancer patients.[21,22] Research subsequently delineated the antioxidant properties of coenzyme Q10.[23,24,25,26,27]
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Proposed mechanisms of action for coenzyme Q10 that are relevant to cancer include its essential function in cellular energy production and its stimulation of the immune system (which may both be related), as well as its role as an antioxidant. Coenzyme Q10 is essential to aerobic energy production,[1,25,28] and it has been suggested that increased cellular energy leads to increased antibody synthesis in B cells (B lymphocytes).[6,18] As noted previously (General Information section), coenzyme Q10 can also behave as an antioxidant.[1,25,26,27,29,30,31,32] In this capacity, coenzyme Q10 is thought to stabilize cell membranes (lipid -containing structures essential to maintaining cell integrity) and to prevent free radical damage to other important cellular components.[1,25,27,32] Free radical damage to DNA (and possibly to other cellular molecules) may be a factor in cancer development.[11,23,30,33,34,35,36]
Pepping J: Coenzyme Q10. Am J Health Syst Pharm 56 (6): 519-21, 1999.
Folkers K, Osterborg A, Nylander M, et al.: Activities of vitamin Q10 in animal models and a serious deficiency in patients with cancer. Biochem Biophys Res Commun 234 (2): 296-9, 1997.
Lockwood K, Moesgaard S, Yamamoto T, et al.: Progress on therapy of breast cancer with vitamin Q10 and the regression of metastases. Biochem Biophys Res Commun 212 (1): 172-7, 1995.
Ren S, Lien EJ: Natural products and their derivatives as cancer chemopreventive agents. Prog Drug Res 48: 147-71, 1997.
Jolliet P, Simon N, Barré J, et al.: Plasma coenzyme Q10 concentrations in breast cancer: prognosis and therapeutic consequences. Int J Clin Pharmacol Ther 36 (9): 506-9, 1998.
Folkers K: The potential of coenzyme Q 10 (NSC-140865) in cancer treatment. Cancer Chemother Rep 2 4 (4): 19-22, 1974.
Folkers K: Relevance of the biosynthesis of coenzyme Q10 and of the four bases of DNA as a rationale for the molecular causes of cancer and a therapy. Biochem Biophys Res Commun 224 (2): 358-61, 1996.
Chipperfield B: Ubiquinone concentrations in some tumour-bearing tissues. Ubiquinone concentrations in tumours and some normal tissues in man. Nature 209 (29): 1207-8, 1966.
Eggens I, Elmberger PG, Löw P: Polyisoprenoid, cholesterol and ubiquinone levels in human hepatocellular carcinomas. Br J Exp Pathol 70 (1): 83-92, 1989.
Mano T, Iwase K, Hayashi R, et al.: Vitamin E and coenzyme Q concentrations in the thyroid tissues of patients with various thyroid disorders. Am J Med Sci 315 (4): 230-2, 1998.
Picardo M, Grammatico P, Roccella F, et al.: Imbalance in the antioxidant pool in melanoma cells and normal melanocytes from patients with melanoma. J Invest Dermatol 107 (3): 322-6, 1996.
Portakal O, Ozkaya O, Erden Inal M, et al.: Coenzyme Q10 concentrations and antioxidant status in tissues of breast cancer patients. Clin Biochem 33 (4): 279-84, 2000.
Bliznakov E, Casey A, Premuzic E: Coenzymes Q: stimulants of the phagocytic activity in rats and immune response in mice. Experientia 26 (9): 953-4, 1970.
Kawase I, Niitani H, Saijo N, et al.: Enhancing effect of coenzyme, Q10 on immunorestoration with Mycobacterium bovis BCG in tumor-bearing mice. Gann 69 (4): 493-7, 1978.
Bliznakov EG: Effect of stimulation of the host defense system by coenzyme Q 10 on dibenzpyrene-induced tumors and infection with Friend leukemia virus in mice. Proc Natl Acad Sci U S A 70 (2): 390-4, 1973.
Bliznakov EG, Adler AD: Nonlinear response of the reticuloendothelial system upon stimulation. Pathol Microbiol (Basel) 38 (6): 393-410, 1972.
Bliznakov EG: Coenzyme Q in experimental infections and neoplasia. In: Folkers K, Yamamura Y, eds.: Biomedical and Clinical Aspects of Coenzyme Q. Vol 1. Amsterdam, The Netherlands: Elsevier/North-Holland Biomedical Press, 1977, pp 73-83.
Folkers K, Shizukuishi S, Takemura K, et al.: Increase in levels of IgG in serum of patients treated with coenzyme Q10. Res Commun Chem Pathol Pharmacol 38 (2): 335-8, 1982.
Folkers K, Hanioka T, Xia LJ, et al.: Coenzyme Q10 increases T4/T8 ratios of lymphocytes in ordinary subjects and relevance to patients having the AIDS related complex. Biochem Biophys Res Commun 176 (2): 786-91, 1991.
Barbieri B, Lund B, Lundström B, et al.: Coenzyme Q10 administration increases antibody titer in hepatitis B vaccinated volunteers--a single blind placebo-controlled and randomized clinical study. Biofactors 9 (2-4): 351-7, 1999.
Shaw M, Ray P, Rubenstein M, et al.: Lymphocyte subsets in urologic cancer patients. Urol Res 15 (3): 181-5, 1987.
Tsuyuguchi I, Shiratsuchi H, Fukuoka M: T-lymphocyte subsets in primary lung cancer. Jpn J Clin Oncol 17 (1): 13-7, 1987.
Yamamoto Y, Yamashita S, Fujisawa A, et al.: Oxidative stress in patients with hepatitis, cirrhosis, and hepatoma evaluated by plasma antioxidants. Biochem Biophys Res Commun 247 (1): 166-70, 1998.
Yamamoto Y, Yamashita S: Plasma ratio of ubiquinol and ubiquinone as a marker of oxidative stress. Mol Aspects Med 18 (Suppl): S79-84, 1997.
Crane FL, Sun IL, Sun EE: The essential functions of coenzyme Q. Clin Investig 71 (8 Suppl): S55-9, 1993.
Overvad K, Diamant B, Holm L, et al.: Coenzyme Q10 in health and disease. Eur J Clin Nutr 53 (10): 764-70, 1999.
Ernster L, Forsmark-Andrée P: Ubiquinol: an endogenous antioxidant in aerobic organisms. Clin Investig 71 (8 Suppl): S60-5, 1993.
Folkers K, Wolaniuk A: Research on coenzyme Q10 in clinical medicine and in immunomodulation. Drugs Exp Clin Res 11 (8): 539-45, 1985.
Beyer RE, Nordenbrand K, Ernster L: The role of coenzyme Q as a mitochondrial antioxidant: a short review. In: Folkers K, Yamamura Y, eds.: Biomedical and Clinical Aspects of Coenzyme Q. Vol 5. Amsterdam, The Netherlands: Elsevier Science Publishers B V (Biomedical Division), 1986, pp 17-24.
Gordon M: Dietary antioxidants in disease prevention. Nat Prod Rep 13 (4): 265-73, 1996.
Palazzoni G, Pucello D, Littarru GP, et al.: Coenzyme Q10 and colorectal neoplasms in aged patients. Rays 22 (1 Suppl): 73-6, 1997 Jan-Mar.
Ernster L, Dallner G: Biochemical, physiological and medical aspects of ubiquinone function. Biochim Biophys Acta 1271 (1): 195-204, 1995.
Aust AE, Eveleigh JF: Mechanisms of DNA oxidation. Proc Soc Exp Biol Med 222 (3): 246-52, 1999.
Halliwell B: Oxygen and nitrogen are pro-carcinogens. Damage to DNA by reactive oxygen, chlorine and nitrogen species: measurement, mechanism and the effects of nutrition. Mutat Res 443 (1-2): 37-52, 1999.
Burcham PC: Internal hazards: baseline DNA damage by endogenous products of normal metabolism. Mutat Res 443 (1-2): 11-36, 1999.
Dreher D, Junod AF: Role of oxygen free radicals in cancer development. Eur J Cancer 32A (1): 30-8, 1996.
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