Melatonin down-regulates HIF-1α expression through inhibition of protein translation in prostate cancer cells

Authors
Jong-Wook ParkMi-Sun HwangSeong-Il SuhWon-Ki Baek
Department
Dept. of Immunology (면역학); Dept. of Microbiology (미생물학)
Issue Date
2009
Citation
Journal of Pineal Research, Vol.46(4) : 415-421, 2009
ISSN
0742-3098
Abstract
Melatonin, the main secretory product of the pineal gland, has been shown to exert an oncostatic activity in cancer cells. Recently, several studies have shown that melatonin has antiangiogenic properties. However, the mechanism by which melatonin exerts antiangiogenenic effects is not understood. Hypoxia inducible factor (HIF)-1 is a transcription factor which mediates adaptive response to changes in tissue oxygenation. HIF-1 is a heterodimer formed by the association of a constitutively expressed HIF-1β subunit and a HIF-1α subunit, the expression of which is highly regulated. In this study, pharmacologic concentrations of melatonin was found to inhibit expression of HIF-1α protein under both normoxic and hypoxic conditions in DU145, PC-3, and LNCaP prostate cancer cells without affecting HIF-1α mRNA levels. Consistent with the reduction in HIF-1α protein levels, melatonin inhibited HIF-1 transcriptional activity and the release of vascular endothelial growth factor. We found that the suppression of HIF-1α expression by melatonin correlated with dephosphorylation of p70S6K and its direct target RPS6, a pathway known to regulate HIF-1α expression at the translational level. Metabolic labeling assays indicated that melatonin inhibits de novo synthesis of HIF-1α protein. Taken together, these results suggest that the pharmacologic concentration of melatonin inhibits HIF-1α expression through the suppression of protein translation in prostate cancer cells.
Keywords
angiogenesisHIF-1amelatoninp70S6Kprostate cancertranslationvascular endothelial cell growth factor
URI
http://kumel.medlib.dsmc.or.kr/handle/2015.oak/34237
Appears in Collections:
1. Journal Papers (연구논문) > 1. School of Medicine (의과대학) > Dept. of Immunology (면역학)
1. Journal Papers (연구논문) > 1. School of Medicine (의과대학) > Dept. of Microbiology (미생물학)
Keimyung Author(s)
박종욱; 서성일; 백원기
Full Text
http://lps3.onlinelibrary.wiley.com.proxy.dsmc.or.kr/doi/abs/10.1111/j.1600-079X.2009.00678.x
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