Inhibitory effects of 5-hydroxy polymethoxyflavones on colon cancer cells.

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).

• Authors: Peiju Qiu, Ping Dong, Huashi Guan, Shiming Li, Chi-Tang Ho, Min-Hsiung Pan, David Julian McClements, Hang Xiao
• Journal: Molecular nutrition & food research (Mol Nutr Food Res) Vol. 54 Suppl 2 Pg. S244-52 (Jul 2010) ISSN: 1613-4133 [Electronic] Germany
• PMID: 20397199 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 5-hydroxy-6,7,8,3',4'-pentamethoxyflavone
• 5-hydroxy-6,7,8,4'-tetramethoxyflavone
• Antineoplastic Agents, Phytogenic
• Flavones
• 5-hydroxy-3,6,7,8,3',4'-hexamethoxyflavone

Topics

• Antineoplastic Agents, Phytogenic (chemistry, pharmacology)
• Apoptosis (drug effects)
• Cell Cycle (drug effects)
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Colonic Neoplasms (drug therapy, metabolism, pathology)
• Drug Screening Assays, Antitumor
• Flavones (chemistry, pharmacology)
• HCT116 Cells
• HT29 Cells
• Humans
• Inhibitory Concentration 50
• Necrosis
• Protein Biosynthesis (drug effects)
• Structure-Activity Relationship