Melatonin abrogates liver, ovarian, and uterine toxicities induced by tamoxifen in a breast cancer mouse model

Abstract

Melatonin is known for its efficacy in breast cancer treatment. However, the safety profile of melatonin, particularly its effect on liver, uterus and ovaries is largely unknown. Here, we explored the safety profile of melatonin using virgin female mice of the Swiss albino strain. Further, we investigated whether melatonin can overcome liver, ovaries and uterine toxicities which are induced by tamoxifen using N,N-dimethylbenzylamine (DMBA) induced breast cancer mouse model? Treatment of tamoxifen after breast cancer induction in mice resulted in reduction of breast masses but severe pathological abnormalities like liver steatosis, hyper ovulation, ovarian cysts, uterine glands dilatations and endometriosis were observed in treated animals. Whereas, melatonin when used in combination with tamoxifen helped to reduce the mouse mammary tumor volume and significantly decreases liver enzymes, steroid hormones and oxidative stress. Melatonin also reverted the liver, ovarian and uterus toxicity induced by tamoxifen. The results have demonstrated that tamoxifen when used as combination therapy with melatonin serve as an effective anti-breast cancer molecule with minimum liver, ovarian and uterus toxicities.