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KMID : 0606920150230040339
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Biomolecules & Therapeutics
2015 Volume.23 No. 4 p.339 ~ p.344
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Anti-Proliferative Effect of Naringenin through p38-Dependent Downregulation of Cyclin D1 in Human Colorectal Cancer Cells
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Song Hun-Min
Park Gwang-Hun
Eo Hyun-Ji
Lee Jin-Wook
Kim Mi-Kyoung
Lee Jeong-Rak
Lee Man-Hyo
Koo Jin-Suk
Jeong Jin-Boo
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Abstract
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Naringenin (NAR) as one of the flavonoids observed in grapefruit has been reported to exhibit an anti-cancer activity. However, more detailed mechanism by which NAR exerts anti-cancer properties still remains unanswered. Thus, in this study, we have shown that NAR down-regulates the level of cyclin D1 in human colorectal cancer cell lines, HCT116 and SW480. NAR inhibited the cell proliferation in HCT116 and SW480 cells and decreased the level of cyclin D1 protein. Inhibition of proteasomal degradation by MG132 blocked NAR-mediated cyclin D1 downregulation and the half-life of cyclin D1 was decreased in the cells treated with NAR. In addition, NAR increased the phosphorylation of cyclin D1 at threonine-286 and a point mutation of threonine-286 to alanine blocked cyclin D1 downregulation by NAR. p38 inactivation attenuated cyclin D1 downregulation by NAR. From these results, we suggest that NAR-mediated cyclin D1 downregulation may result from proteasomal degradation through p38 activation. The current study provides new mechanistic link between NAR, cyclin D1 downregulation and cell growth in human colorectal cancer cells.
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KEYWORD
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Naringenin, Cyclin D1, Cancer chemoprevention, Human colorectal cancer
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