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Involvement of HIF‐1 Pathway in Regulation of p27/kip1 and p21/cip1 by Oxidative Stress and Antioxidant
Author(s) -
KIM JongSang,
Quintos Lesley,
LEE In Ae,
LIM JiSun,
SEO JiYeon,
KIM Hak Ryul,
Sung MiKyung,
Yoon Park Jung Han
Publication year - 2009
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.23.1_supplement.565.2
Subject(s) - hydrogen peroxide , oxidative stress , pi3k/akt/mtor pathway , protein kinase b , chemistry , microbiology and biotechnology , delphinidin , western blot , cell growth , cell cycle , signal transduction , antioxidant , cell , biology , biochemistry , cyanidin , gene
Our previous proteomic study showed that oxidative stress to HT29 human colon cancer cells suppressed expression of p27/kip1 and p21 while cotreatment with delphinidin, an antioxidant, restored the normal level or enhanced their expression. Current study was conducted to confirm the regulation of these proteins using in vivo system. ICR mice were injected with varying concentrations of hydrogen peroxide, delphinidin and both. Western blot analysis for the mouse large intestinal tissue showed that both p27/kip1 and p21 expression was downregulated by hydrogen peroxide in a dose dependent manner, but was enhanced by combined treatment with hydrogen peroxide and delphinidin. Same results were observed using HCT 116 cells. Furthermore, suppression of cell proliferation by delphinidin appears to be associated with enhanced expression of p27/kip1 and p21, two major components responsible for cell cycle arrest. Our data are consistent with the hypothesis that the levels of these proteins are modulated by C‐myc activity via regulation of HIF‐1 level which is, in turn, governed by its upstream regulators comprising of mTOR/AkT/PI3K signaling pathway. In conclusion, HIF‐1alpha appears to play an important role in the regulation of cell cycle regulator proteins, and thereby may be a good target for cancer prevention.