Melatonin: A Potential Antineoplastic Agent in Breast Cancer.

Melatonin is primarily synthesized in the pineal gland under the influence of noradrenergic stimulation at night. It regulates the sleep-wake cycle, gonadal activity, redox homeostasis, immune functions, and anticarcinogenic effects at the normal physiological state. The activity of melatonin is mediated by membrane-bound G protein-coupled receptors MT1 and MT2. Circadian deregulation, exposure to light-at-night, shift work, and jet lag disrupt the melatonin rhythm. A low level of circulatory melatonin concentration influences the development of many cancers, including breast cancer. Melatonin acts as an anticancer agent in breast tissue. It suppresses metabolic activity, regulates cell-signaling pathways, and subsequently blocks cell proliferation. This indolamine induces apoptosis, inhibits chronic inflammation and metastasis. Melatonin restricts the functions of estrogen receptor α and also inhibits aromatase activity. Melatonin is a potent antioxidant that reduces the chemoresistance capacity of breast cancer cells. At therapeutic levels, it potentially increases the efficacy of chemotherapeutic agents and decreases their adverse effects during the treatment of breast cancer. The present review focuses on the antineoplastic activity of melatonin against breast cancer. Emphasis has been given to the possible use of melatonin in the treatment of breast cancer.