Abstract:The prognostic significance of supplementing co-enzyme Q 10 (CoQ 10 ), riboflavin and niacin (CoRN) along with tamoxifen to breast cancer patients was evaluated by measuring the serum cytokine levels of interleukin (IL)-1 β , IL-6, IL-8, tumour necrosis factor α (TNF-α ) and vascular endothelial growth factor. In the present study, 84 breast cancer patients were randomized to receive a daily supplement of CoQ 10 100 mg, riboflavin 10 mg and niacin 50 mg, one dosage per day along with tamoxifen 10 mg twice a day. Serum cytokine levels were elevated in untreated breast cancer patients (Group II) and significantly reduced after tamoxifen therapy for more than 1 year (Group III). When group III breast cancer patients were supplemented with CoRN for 45 days (Group IV) and 90 days (Group V) along with tamoxifen, a significant reduction in cytokine levels were observed (P < 0.05). Such a decrease in serum cytokine levels after CoRN supplementation in breast cancer patients may suggest good prognosis and efficacy of the treatment, and might even offer protection from metastases and recurrence of cancer.

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Breast cancer is a major public-health issue worldwide and according to estimates in 2002, there were 1151298 new cases of breast cancer diagnosed and 410712 deaths caused by breast cancer and more than 4 · 4 million women living with breast cancer worldwide.1) The antitumour activity of tamoxifen (TAM) is due to its occupation in the intracellular estrogen receptor sites of the target tissue and blocking the action of biologically active estrogen and estradiol.2) In addition, the antiproliferative effects of TAM may relate to its inhibition of protein kinase C 3) and it's binding to calmodulin, a protein that plays a role in DNA synthesis.4) A complicating factor is the relapse in breast cancer patients undergoing tamoxifen therapy. In this subset of patients, treatment is only palliative and recurrent breast cancer is incurable. 5)CoQ 10 or ubiquinone is a lipid-soluble component of virtually all cell membranes and has an important role in the respiratory metabolism as a mobile electron and proton carrier in the mitochondrial electron transport chain. 6) CoQ 10 also functions as an antioxidant, which protects the cells both directly by preventing lipid peroxidation and indirectly by regenerating other antioxidants such as ascorbate and a-tocopherol. 7) CoQ 10 increases the phagocytic activity in tumour induced mice and is found to increase the levels of IgG 8) and decrease the levels of circulating tumour necrosis factor-a and interleukin-6. 9) Riboflavin, in its active coenzymic forms like flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), participates in oxidation-reduction reactions in numerous metabolic pathways and in energy production via the respiratory chain.10) Riboflavin captures reactive metabolites like tamoxifen and carcinogens to form a complex and thereby, prevents formation of DNA adducts, 11) prevents DNA methylation and maintains genomic stability. 12,13) Niacin and its co-factors, nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP), are essential for a variety of oxidation-reduction reactions that comprise tissue respiration.14) The protective effect of nicotinamide may be due to its action as a free radical scavenger. 15) Niacin participates in DNA synthesis and acts as substrate for enzyme poly(ADP-ribose) polymerase-1 (PARP-1) which produces poly(ADP-ribose). The enzyme PARP-1 is associated with base excision repair, cellular differentiation, gene expression and plays a role in p53 expression and activation. Hence, riboflavin is important for protecting normal cell from genetic toxicity for maintaining genomic stability while remaining cytotoxic to neoplastic cells. 16,17) Studies from our laboratory with CoRN supplementation to TAM in murine model have established antitumour activity of the drug by increasing the expression of tumour suppressor gene MnSOD. CoRN supplementation restored lipid peroxide levels and activities of enzymic and non-enzymic antioxidants to near normalcy in rat mammary carcinoma and thus proving its mitoch...

The antioxidant defense system is compromised in breast cancer patients. There is a shift in the oxidant / antioxidant balance in favor of lipid peroxidation (LPO), which could lead to tumour promotion observed in the disease. CT of CoQ(10), Niacin and Riboflavin along with TAM significantly increased the AO status, while decreasing lipid and lipid peroxides. The results suggest the necessity of therapeutic co-administration of antioxidants along with conventional drug to such patients. However, due to limited number of cases included in this study, more studies may be required to substantiate the results and arrive at a definitive conclusion, in terms of safety and efficacy of adding an AO therapy in treatment of breast cancer.