ABSTRACT
Despite advances in cancer therapy, the mortality has increased 5.5% in 7 years. This therapy increased cure rates and survival time. Survivors have increased risk of recurrence of primary tumor, and development of a new cancer and nonneoplastic diseases. MicroRNAs act as oncogenes or antioncogenes. Individual or multiple antioxidants administered during standard therapy did not significantly improve treatment outcomes or reduce side effects. This could have been due to use of preventive doses of antioxidants that stimulate cancer growth and protect cancer cells during therapy. Cancer cells constitutively express high levels of Nrf2 allowing cell proliferation and preventing apoptosis, and making them resistant to therapy by elevating cytoprotective enzymes. Therapeutic doss of antioxidants activates Nrf2 and inhibits tumor growth. This paradoxical effect of antioxidants are explained by the studies in which antioxidants bypass the protective effect of Nrf2 and induce apoptosis by enhancing the expression of apoptotic genes, reducing the levels or interfere Nrf2 function, and by altering the expression of microRNAs and their target proteins that cause growth inhibition. A mixture of therapeutic doses of antioxidants to be administered orally before, during, and entire treatment period is proposed for testing by clinical investigation for its safety and efficacy.
