Induction of GADD45α expression contributes to the anti-proliferative effects of polymethoxyflavones on colorectal cancer cells

Andy Chi Lung Lee, Wei Chun Hsiao, Duncan Edward Wright, Shin Yen Chong, Siew Keng Leow, Chi Tang Ho, Cheng Fu Kao, Yi Chen Lo

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

Polymethoxyflavones (PMFs), such as nobiletin and tangeretin, have a high cellular uptake rate, on account of their hydrophobicity. Nobiletin has been shown to down-regulate inflammatory gene expression, and is thus considered a promising anti-inflammatory and anti-carcinogenic agent. Most proteins known to be affected by PMFs are cell cycle regulators and kinases. In the present study, we demonstrate that PMF-mediated induction of GADD45α partially underlies the anti-proliferative effect of PMF on colorectal cancer cells. PMF-mediated induction of GADD45α was found to be associated with chromatin remodeling events at a novel enhancer element residing at intron 1 of GADD45α. Moreover, GADD45α transcription correlated with differential acetylation of lysines 14 and 27 of histone H3 (H3K14/27) following treatment with either nobiletin or tangeretin. PMF-induced changes in H3K27 acetylation, H2A.Z and CBP were observed at intron 1, but not at p53 response-elements of GADD45α, suggesting that nobiletin/tangeretin-mediated GADD45α activation may be independent of p53.

Original languageEnglish (US)
Pages (from-to)616-624
Number of pages9
JournalJournal of Functional Foods
Volume5
Issue number2
DOIs
StatePublished - Apr 2013

All Science Journal Classification (ASJC) codes

  • Food Science
  • Medicine (miscellaneous)
  • Nutrition and Dietetics

Keywords

  • Epigenetic regulation
  • GADD45α
  • Nobiletin
  • Polymethoxyflavones
  • Tangeretin

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