Illuminating the Tug-of-War between Estrogen and Melatonin in Estrogen Receptor Positive Breast Cancer Progression

Abstract

Estrogen, an endogenous female sex hormone, plays a significant role in promoting the progression of estrogen receptor positive (ER+) breast cancer cells by enhancing proliferation, inhibiting apoptosis, and facilitating invasion and metastasis. Conversely, melatonin, a hormone with well-documented anti-tumourigenic properties, demonstrates the ability to counteract these cancer-promoting effects. Dysregulated estrogen and melatonin levels have been shown to increase breast cancer risk. Additionally, both hormones decline during ageing and it has been hypothesised that ageing associated decline in melatonin is a risk factor for cancer. While the individual effects of estrogen and melatonin on cancer have been extensively studied, emerging evidence suggests that these hormones exert opposing influences on various cancer hallmarks. To explore this phenomenon, we conducted a study using the MCF-7 ER+ breast adenocarcinoma cell line to investigate whether melatonin can attenuate the protumourigenic effects exerted by 17β-estradiol (E2). Our findings revealed that E2 stimulated cell proliferation and migration, whereas the addition of melatonin attenuated these effects. Moreover, the combination of melatonin with E2 demonstrated a potential to promote apoptosis in breast cancer cells. These results shed light on the capacity of melatonin to mitigate the protumourigenic effects of estrogen in ER+ breast cancer cells. Importantly, it opens new avenues for considering melatonin supplementation as a preventive and therapeutic strategy for ER+ breast cancer in menopausal individuals and those with cancer. Future studies should delve deeper into these findings to fully comprehend the underlying mechanisms and establish the clinical relevance of melatonin in breast cancer prevention and treatment.

Keywords: melatonin, Breast cancer, estrogen, cancer prevention