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Melatonin treatment induces interplay of apoptosis, autophagy, and senescence in human colorectal cancer cells
Author(s) -
Hong Yunkyung,
Won Jinyoung,
Lee Youngjeon,
Lee Seunghoon,
Park Kanghui,
Chang KyuTae,
Hong Yonggeun
Publication year - 2014
Publication title -
journal of pineal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 131
eISSN - 1600-079X
pISSN - 0742-3098
DOI - 10.1111/jpi.12119
Subject(s) - melatonin , apoptosis , programmed cell death , endocrinology , population , cardiotoxicity , medicine , melatonin receptor , biology , senescence , autophagy , cancer research , cell cycle , toxicity , biochemistry , environmental health
In A sia, the incidence of colorectal cancer has been increasing gradually due to a more W esternized lifestyle. The aim of study is to determine the interaction between melatonin‐induced cell death and cellular senescence. We treated HCT 116 human colorectal adenocarcinoma cells with 10 μ m melatonin and determined the levels of cell death‐related proteins and evaluated cell cycle kinetics. The plasma membrane melatonin receptor, MT 1, was significantly decreased by melatonin in a time‐dependent manner, whereas the nuclear receptor, ROR α , was increased only after 12 hr treatment. HCT 116 cells, which upregulated both pro‐apoptotic B ax and anti‐apoptotic B cl‐xL in the early response to melatonin treatment, activated autophagic as well as apoptotic machinery within 18 hr. Melatonin decreased the S‐phase population of the cells to 57% of the control at 48 hr, which was concomitant with a reduction in BrdU‐positive cells in the melatonin‐treated cell population. We found not only marked attenuation of E‐ and A‐type cyclins, but also increased expression of p16 and p‐p21. Compared to the cardiotoxicity of Trichostatin A in vitro, single or cumulative melatonin treatment induced insignificant detrimental effects on neonatal cardiomyocytes. We found that 10 μ m melatonin activated cell death programs early and induced G1‐phase arrest at the advanced phase. Therefore, we suggest that melatonin is a potential chemotherapeutic agent for treatment of colon cancer, the effects of which are mediated by regulation of both cell death and senescence in cancerous cells with minimized cardiotoxicity.