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Hydroxylated polymethoxyflavones induce p53 and Bax dependent apoptosis and cell cycle arrest.
Author(s) -
Qiu Peiju,
Guan Huashi,
Dong Ping,
Li Shiming,
Ho ChiTang,
Pan MinHsiung,
McClements David Julian,
Xiao Hang
Publication year - 2010
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.24.1_supplement.lb484
Subject(s) - apoptosis , cell cycle checkpoint , cell cycle , null cell , microbiology and biotechnology , chemistry , cell , bcl 2 associated x protein , population , biology , programmed cell death , cancer research , caspase 3 , cell culture , biochemistry , medicine , genetics , environmental health
Previously, we reported that hydroxylated polymethoxyflavones (OH‐PMFs, such as 5‐hydroxy‐6,7,8,3′,4′‐pentamethoxyflavone (5HPMF), 5‐hydroxy‐3,6,7,8,3′,4′‐hexamethoxyflavone (5HHMF), and 5‐hydroxy‐6,7,8,4′‐tetramethoxyflavone (5HTMF) potently induced apoptosis and cell cycle arrest in HCT116 colon cancer cells. Herein, using isogenetic variants of HCT116 cells, we investigated the effects of p53 and BAX status on the apoptosis and cell cycle arrest induced by OH‐PMFs. All three OH‐PMFs increased G0/G1 cell population in wt‐ p53 and these effects were abolished in null‐p53 HCT116 cells. In null‐p21 HCT116 cells, none of the three OH‐PMFs induced G0/G1 arrest. These results suggest that OH‐PMFs induce G0/G1 arrest by a p53 and p21 dependent manner. 5HHMF and 5HTMF can significantly induce apoptosis in wt‐ p53 cells, but not in null‐p53 cells. Moreover, 5HHMF and 5HTMF significantly induced apoptosis in BAX(+/−) HCT116 cells, while their pro‐apoptotic effects on BAX(−/−) HCT116 cells were marginal. Western blot analysis showed that 5HHMF and 5HTMF increased the levels of p21, cleaved caspase‐3, cleaved PARP in both wt‐ p53 and BAX(+/−) HCT116 cells, and these effects were much weaker in null‐p53 and BAX(−/−) HCT116 cells. Taken together, our results demonstrated that OH‐PMFs, especially 5HHMF and 5HTMF induce apoptosis and cell cycle arrest by a p53 and BAX dependent manner.