Melatonin treatment induces interplay of apoptosis, autophagy, and senescence in human colorectal cancer cells

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Title
Melatonin treatment induces interplay of apoptosis, autophagy, and senescence in human colorectal cancer cells
Author(s)
Y Hong; J Won; Youngjeon Lee; S Lee; K Park; Kyu Tae Chang; Y Hong
Bibliographic Citation
Journal of Pineal Research, vol. 56, no. 3, pp. 264-274
Publication Year
2014
Abstract
In Asia, the incidence of colorectal cancer has been increasing gradually due to a more Westernized lifestyle. The aim of study is to determine the interaction between melatonin-induced cell death and cellular senescence. We treated HCT116 human colorectal adenocarcinoma cells with 10 μm melatonin and determined the levels of cell death-related proteins and evaluated cell cycle kinetics. The plasma membrane melatonin receptor, MT1, was significantly decreased by melatonin in a time-dependent manner, whereas the nuclear receptor, RORα, was increased only after 12 hr treatment. HCT116 cells, which upregulated both pro-apoptotic Bax and anti-apoptotic Bcl-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 μm 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
Keyword
apoptosisautophagycardiotoxicitymelatoninsenescence
ISSN
0742-3098
Publisher
Wiley
DOI
http://dx.doi.org/10.1111/jpi.12119
Type
Article
Appears in Collections:
Ochang Branch Institute > Division of National Bio-Infrastructure > National Primate Research Center > 1. Journal Articles
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