Exogenous melatonin leads to the activation of autophagy and cellular senescence in colorectal cancer cells

The purpose of the present study was to determine the anti‐cancer effect of melatonin on HCT116 colorectal cancer cells. At 10 μM, melatonin induced a significant reduction in MT‐R1A expression and an increase in RORα expression over time ( p <.01). Proliferation was strikingly reduced by 10 μM melatonin in a time‐dependent manner. Bcl‐2 mRNA expression was decreased at 48 h after treatment ( p <.01). Furthermore, the induction of cleaved caspase 3, a significant increase in converted LC3II, and a decrease in Bcl‐1 expression were observed in response to melatonin treatment ( p <.01). A time‐dependent increase in the number of cells in G1 phase was also caused by melatonin at 10 μM. Cyclin D expression was unchanged, whereas cyclin E expression was significantly reduced by melatonin at 10 μM ( p <.01). The level of cyclin‐dependent kinase inhibitors, p16 was also altered in melatonin‐treated HCT116 cells. Treatment with melatonin at a pharmacologic concentration significantly inhibited the overgrowth of HCT116 cells, but activated by stress‐induced senescence as well as autophagy indicating it could be useful chemotherapeutic drug with minimal cytotoxicity. Funding: BioGreen21 Program (Code No. 20070401‐034‐006‐009‐02‐00), Rural Development Administration, Korea