Investigation of the effect of melatonin used as a co-treatment with doxorubicin in MCF-7 human breast cancer cells

Abstract

Melatonin, produced by the pineal gland, has anti-proliferative and cytotoxic effects in many kinds of tumors. Most of its oncostatic actions have been characterized in hormone dependent breast cancer. Melatonin reduces the incidence and growth of mammary tumors in rodents and inhibits proliferation and invasiveness of estrogen responsive breast cancer cells. Many studies suggest that melatonin is a good co-treatment with conventional chemotherapeutic drugs. It has protective effects in normal tissues palliating side effects and also enhancing cytotoxicity and apoptotic responses induced by chemotherapeutic agents. The molecular pathways modified by melatonin and triggered by chemotherapeutic drugs remain largely unknown. Doxorubicin is an anthracycline that inhibits DNA and RNA synthesis, currently used in chemotherapy. Melatonin enhances doxorubicin cytotoxicity in different kinds of cancer. In estrogen responsive human cancer cells, melatonin and doxorubicin have synergic effects on apoptosis. In this study, we demonstrated that physiological concentrations (1nM) of melatonin enhanced the anti-proliferative effect of low doses of doxorubicin in breast cancer cells. Additionally, we identified changes in gene expression induced by doxorubicin at concentrations equivalent to those employed in therapy (1 M), and found that melatonin reverted the effect of doxorubicin in CDKN1A and TWIST1 expression, two genes altered in breast carcinogenesis