title: Anti-Proliferative Effect of Naringenin through p38-Dependent Downregulation of Cyclin D1 in Human Colorectal Cancer Cells.
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.
authors.affiliation: Department of Bioresource Sciences, Andong National University, Andong 760-749.
authors.forename: Hun Min
authors.initials: HM
authors.lastname: Song
authors.affiliation: Department of Bioresource Sciences, Andong National University, Andong 760-749.
authors.forename: Gwang Hun
authors.initials: GH
authors.lastname: Park
authors.affiliation: Department of Bioresource Sciences, Andong National University, Andong 760-749.
authors.forename: Hyun Ji
authors.initials: HJ
authors.lastname: Eo
authors.affiliation: Department of Bioresource Sciences, Andong National University, Andong 760-749.
authors.forename: Jin Wook
authors.initials: JW
authors.lastname: Lee
authors.affiliation: Department of Bioresource Sciences, Andong National University, Andong 760-749.
authors.forename: Mi Kyoung
authors.initials: MK
authors.lastname: Kim
authors.affiliation: Gyeongbuk Institute for Bio-industry, Andong 760-380.
authors.forename: Jeong Rak
authors.initials: JR
authors.lastname: Lee
authors.affiliation: Gyeongbuk Institute for Bio-industry, Andong 760-380.
authors.forename: Man Hyo
authors.initials: MH
authors.lastname: Lee
authors.affiliation: Department of Bioresource Sciences, Andong National University, Andong 760-749 ; Insititute of Agricultural Science and Technology, Andong National University, Andong 760-749, Republic of Korea.
authors.forename: Jin Suk
authors.initials: JS
authors.lastname: Koo
authors.affiliation: Department of Bioresource Sciences, Andong National University, Andong 760-749 ; Insititute of Agricultural Science and Technology, Andong National University, Andong 760-749, Republic of Korea.
authors.forename: Jin Boo
authors.initials: JB
authors.lastname: Jeong
keywords: Cancer chemoprevention; Cyclin D1; Human colorectal cancer; Naringenin