Document Detail


Inhibitory effects of 5-hydroxy polymethoxyflavones on colon cancer cells.
MedLine Citation:
PMID:  20397199     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Molecular nutrition & food research     Volume:  54 Suppl 2     ISSN:  1613-4133     ISO Abbreviation:  Mol Nutr Food Res     Publication Date:  2010 Jul 
Date Detail:
Created Date:  2010-07-29     Completed Date:  2010-12-08     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101231818     Medline TA:  Mol Nutr Food Res     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  S244-52     Citation Subset:  IM    
Affiliation:
Marine Drug and Food Institute, Ocean University of China, Qingdao Shandong, P R China.
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MeSH Terms
Descriptor/Qualifier:
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
Chemical
Reg. No./Substance:
0/5-hydroxy-3,6,7,8,3',4'-hexamethoxyflavone; 0/5-hydroxy-6,7,8,3',4'-pentamethoxyflavone; 0/5-hydroxy-6,7,8,4'-tetramethoxyflavone; 0/Antineoplastic Agents, Phytogenic; 0/Flavones

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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