Premium
Exogenous melatonin leads to the activation of autophagy and cellular senescence in colorectal cancer cells
Author(s) -
Hong Yunkyung,
Kim Sunmi,
Park Sookyoung,
Hong Yonggeun
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.lb657
Subject(s) - melatonin , autophagy , endocrinology , medicine , senescence , cancer cell , kinase , apoptosis , colorectal cancer , chemistry , biology , cancer research , cancer , microbiology and biotechnology , biochemistry
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