The p53-, Bax- and p21-dependent inhibition of colon cancer cell growth by 5-hydroxy polymethoxyflavones

Peiju Qiu, Huashi Guan, Ping Dong, Shiming Li, Chi Tang Ho, Min Hsiung Pan, David Julian Mcclements, Hang Xiao

Research output: Contribution to journalArticlepeer-review

46 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)613-622
Number of pages10
JournalMolecular Nutrition and Food Research
Volume55
Issue number4
DOIs
StatePublished - Apr 2011

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Food Science

Keywords

  • 5-Hydroxy polymethoxyflavones
  • Bax
  • Colon cancer
  • P21
  • P53

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