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The p53‐, Bax‐ and p21‐dependent inhibition of colon cancer cell growth by 5‐hydroxy polymethoxyflavones
Author(s) -
Qiu Peiju,
Guan Huashi,
Dong Ping,
Li Shiming,
Ho ChiTang,
Pan MinHsiung,
McClements David Julian,
Xiao Hang
Publication year - 2011
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.201000269
Subject(s) - apoptosis , annexin , chemistry , cell cycle , cell , cell cycle checkpoint , cancer research , population , cancer cell , microbiology and biotechnology , biology , cancer , biochemistry , medicine , genetics , environmental health
Scope: Previously, we reported that 5‐hydroxy polymethoxyflavones (5OH‐PMFs) isolated from orange, namely 5‐hydroxy‐6,7,8,3′,4′‐pentamethoxyflavone, 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 multiple human colon cancer cells. Herein, using isogenic variants of HCT116 human colon cancer cells, we investigated the effects of p53, Bax and p21 on the apoptosis and cell‐cycle arrest induced by different 5OH‐PMFs. Methods and results: Annexin V/PI co‐staining assay demonstrated that 5HHMF and 5HTMF significantly induced apoptosis in HCT116 (p53 +/+ ) cells but not in HCT116 (p53 −/− ) cells. Furthermore, 5HHMF and 5HTMF significantly induced apoptosis in HCT116 (Bax +/− ) cells, whereas their pro‐apoptotic effects on HCT116 (Bax −/− ) cells were marginal. All three 5OH‐PMFs increased G0/G1 cell population of HCT116 (p53 +/+ ) cells, and these effects were abolished in HCT116 (p53 −/− ) and HCT116 (p21 −/− ) cells. Immunoblotting analysis showed that 5HHMF and 5HTMF increased the levels of cleaved caspase‐3, cleaved PARP in both HCT116 (p53 +/+ ) and HCT116 (Bax +/− ) cells and these effects were much weaker in HCT116 (p53 −/− ) and HCT116 (Bax −/− ) cells. Conclusion: Our results demonstrated that 5OH‐PMFs, especially 5HHMF and 5HTMF, induce apoptosis and cell‐cycle arrest by p53‐, Bax‐ and p21‐dependent mechanism.