Inhibitory effects of 5-hydroxy polymethoxyflavones on colon cancer cells

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

Research output: Contribution to journalArticlepeer-review

92 Scopus citations

Abstract

Hydroxylated polymethoxyflavones (PMFs) are a class of novel flavonoid compounds mainly found in citrus plants. We studied the effects of three major 5-hydroxy PMFs, namely: 5-hydroxy-6,7,8,3′,4′-pentamethoxyflavone, 5-hydroxy-3,6,7,8,3′,4′-hexamethoxyflavone, and 5-hydroxy-6,7,8,4′-tetramethoxyflavone, on human colon cancer HCT116 and HT29 cells. Their effects were compared with those produced by their permethoxylated counterparts, namely: nobiletin, 3,5,6,7,8,3′,4′-heptamethoxylflavone, and tangeretin. 5-Hydroxy PMFs showed much stronger inhibitory effects on the growth of the colon cancer cells in comparison with their permethoxylated counterparts, suggesting the pivotal role of hydroxyl group at 5-position in the enhanced inhibitory activity by 5-hydroxy PMFs. Flow cytometry analysis demonstrated that three 5-hydroxy PMFs produced different effects on the cell cycle and apoptosis, which may suggest that three 5-hydroxy PMFs act through different mechanisms. For example, 5-hydroxy-6,7,8,3′,4′-pentamethoxyflavone caused cell cycle arrest at G2/M phase in HT29 cells, while 5-hydroxy-3,6,7,8,3′,4′-hexamethoxyflavone led to significant G0/G1 phase arrest. In contrast, 5-hydroxy-6,7,8,4′-tetramethoxyflavone increased sub-G0/G1 cell population, which has been confirmed to be due to enhanced apoptosis. Our results further demonstrated that the inhibitory effects of 5-hydroxy PMFs were associated with their ability in modulating key signaling proteins related to cell proliferation and apoptosis, such as p21 Cip1/Waf1, CDK-2, CDK-4, phosphor-Rb, Mcl-1, caspases 3 and 8, and poly ADP ribose polymerase (PARP).

Original languageEnglish (US)
Pages (from-to)S244-S252
JournalMolecular Nutrition and Food Research
Volume54
Issue numberSUPPL. 2
DOIs
StatePublished - Jul 2010

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Food Science

Keywords

  • 5-hydroxy polymethoxyflavones
  • Apoptosis
  • Cell cycle arrest
  • Cell growth inhibition
  • Colon cancer

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