Inhibitory effects of 5-hydroxy polymethoxyflavones on colon cancer cells

✍ Scribed by Peiju Qiu; Ping Dong; Huashi Guan; Shiming Li; Chi-Tang Ho; Min-Hsiung Pan; David Julian McClements; Hang Xiao

• Publisher: John Wiley and Sons
• Year: 2010
• Tongue: English
• Weight: 388 KB
• Volume: 54
• Category: Article
• ISSN: 1613-4125
• DOI: 10.1002/mnfr.200900605

✦ Synopsis

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).