Melatonin and cisplatin synergistically enhance apoptosis via autophagy-dependent alteration of P53 transcription in human colorectal cancer cells

Abstract

Cisplatin is one of the most general chemotherapeutic agents used to treat various cancers, including colorectal and breast cancer. because cisplatin has some adverse effects including cardiotoxicity and hepatoxicity, it is usage limited.  Melatonin is a natural product that responsible for regulator of circadian rhythms and has anti-cancer potential. However, its synergistic effects with melatonin and cisplatin, its efficacy in cancer cell death, its mechanisms and biological targets are not well understood. In this study, it was aimed to determine the synergistic activity of cisplatin with melatonin in colon cancer cell death through apoptotic and autophagic mechanisms. In the present study, we found that melatonin with cisplatin treatment did not affect the cytotoxicity, but cisplatin increased in 24 h incubation period. Melatonin and combined treatment of melatonin and cisplatin also increased the cytotoxicity in 48h incubation period. It was observed that cisplatin treatments used together with melatonin and melatonin inhibited the mitogen activity of colon cancer cells. In addition, combined treatment of cisplatin and melatonin and single treatment of cisplatin increased both apoptosis and autophagic cell death. The results revealed that the use of melatonin with combined cisplatin has been shown to increase the apoptosis and autophagic cell deaths via P53 gene activation.