Melatonin-induced KiSS1 expression inhibits triple-negative breast cancer cell invasiveness.

Breast cancer is one of the most common types of cancer in women, and its metastasis increases the risk of mortality. Melatonin, a hormone that regulates the circadian rhythm, has been revealed to inhibit breast cancer growth and metastasis. However, its involvement in highly metastatic triple-negative breast cancer cells is yet to be elucidated. The present study demonstrated that melatonin inhibited the metastatic abilities of triple-negative breast cancer cells and prolonged its inhibitory effect via the expression of kisspeptin (KiSS1), which is a suppressor of metastasis. Melatonin at concentrations ranging from 1 nM to 10 µM did not affect the proliferation of metastatic MDA-MB-231 and HCC-70 triple-negative breast cancer cells. However, melatonin repressed invasiveness in triple-negative breast cancer cells. Additionally, conditional medium from melatonin-treated MDA-MB-231 cells repressed the invasiveness of triple-negative breast cancer cells. Melatonin promoted the production of KiSS1, a metastasis suppressor encoded by the KiSS1 gene. In addition, melatonin increased KiSS1 expression via the expression and transcriptional activation of GATA binding protein 3. Silencing of KiSS1 weakened melatonin inhibition of breast cancer cell invasiveness. Therefore, the present study concluded that melatonin activates KiSS1 production in metastatic breast cancer cells, suggesting that melatonin activation of KiSS1 production may regulate the process of breast cancer metastasis.