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Anti-Proliferative Effect of Naringenin through p38-Dependent Downregulation of Cyclin D1 in Human Colorectal Cancer Cells

  • Song, Hun Min (Department of Bioresource Sciences, Andong National University) ;
  • Park, Gwang Hun (Department of Bioresource Sciences, Andong National University) ;
  • Eo, Hyun Ji (Department of Bioresource Sciences, Andong National University) ;
  • Lee, Jin Wook (Department of Bioresource Sciences, Andong National University) ;
  • Kim, Mi Kyoung (Department of Bioresource Sciences, Andong National University) ;
  • Lee, Jeong Rak (Gyeongbuk Institute for Bio-industry) ;
  • Lee, Man Hyo (Gyeongbuk Institute for Bio-industry) ;
  • Koo, Jin Suk (Department of Bioresource Sciences, Andong National University) ;
  • Jeong, Jin Boo (Department of Bioresource Sciences, Andong National University)
  • Received : 2015.03.02
  • Accepted : 2015.04.22
  • Published : 2015.07.01

Abstract

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.

Keywords

Acknowledgement

Supported by : Andong National University, National Research Foundation of Korea (NRF)

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