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Induction of the tumor suppressor protein p53 contributes to fisetin‐induced Bax translocation to mitochondria and apoptosis of HCT‐116 colon cancer cells
Author(s) -
Lim Doyoung,
Park Jung Han Yoon
Publication year - 2008
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.22.1_supplement.700.32
Subject(s) - fisetin , apoptosis , western blot , mitochondrion , poly adp ribose polymerase , microbiology and biotechnology , chemistry , chromosomal translocation , cancer research , biology , biochemistry , gene , polymerase , flavonoid , antioxidant
Fisetin, a flavonol, has been reported to have anti‐cancer properties. In the previous study, we have demonstrated that fisetin induces apoptosis of human colon cancer cells via activation of caspase‐8 and alteration of Bcl‐2 family proteins. In the present study, we examined the role of p53 tumor suppressor protein in fisetin‐induced apoptosis of HCT‐116 cells. Treatment of HCT‐116 cells with fisetin led to a dose‐dependent increase in p53 and decrease in mdm‐2 protein levels. Reporter gene analysis using a luciferase plasmid containing direct repeats of the transcription recognition sequences for p53 indicated that p53 reporter activity was significantly increased in fisetin‐treated cells. Subcellular fractionation and Western blot analysis, and immunocytochemistry revealed that inhibition of p53 expression by small interference of RNA decreased fisetin‐induced Bax translocation to mitochondria. In addition, inhibition of p53 expression significantly reduced fisetin‐induced chromatin condensation and cleavage of poly(ADP‐ribose) polymerase. These results indicate that induction of p53 led to Bax translocation to mitochondria, which contributes to apoptosis in fisetin‐treated HCT‐116 cells.