Document Detail

Tangeretin and nobiletin induce G1 cell cycle arrest but not apoptosis in human breast and colon cancer cells.
MedLine Citation:
PMID:  17197076     Owner:  NLM     Status:  MEDLINE    
Tangeretin and nobiletin are citrus flavonoids that are among the most effective at inhibiting cancer cell growth in vitro and in vivo. The antiproliferative activity of tangeretin and nobiletin was investigated in human breast cancer cell lines MDA-MB-435 and MCF-7 and human colon cancer line HT-29. Both flavonoids inhibited proliferation in a dose- and time-dependent manner, and blocked cell cycle progression at G1 in all three cell lines. At concentrations that resulted in significant inhibition of proliferation and cell cycle arrest, neither flavonoid induced apoptosis or cell death in any of the tumor cell lines. To test the ability of arrested cells to recover, cells that were incubated with tangeretin and nobiletin for 4 days were then cultured in flavonoid-free medium for an additional 4 days. Cells resumed proliferation similar to untreated control within a day of flavonoid removal. Cell cycle distribution was similar to that of control within 4 days of flavonoid removal. These data indicate that, in these cell lines at concentrations that inhibit proliferation up to 80% over 4 days, tangeretin and nobiletin are cytostatic and significantly suppress proliferation by cell cycle arrest without apoptosis. Such an agent could be expected to spare normal tissues from toxic side effects. Thus, tangeretin and nobiletin could be effective cytostatic anticancer agents. Inhibition of proliferation of human cancers without inducing cell death may be advantageous in treating tumors as it would restrict proliferation in a manner less likely to induce cytotoxicity and death in normal, non-tumor tissues.
Karen L Morley; Peter J Ferguson; James Koropatnick
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-01-02
Journal Detail:
Title:  Cancer letters     Volume:  251     ISSN:  0304-3835     ISO Abbreviation:  Cancer Lett.     Publication Date:  2007 Jun 
Date Detail:
Created Date:  2007-04-23     Completed Date:  2007-06-28     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7600053     Medline TA:  Cancer Lett     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  168-78     Citation Subset:  IM    
Cancer Research Laboratory Program, London Regional Cancer Program, Lawson Health Research Institute, London Health Sciences Centre, London, Ont., Canada.
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MeSH Terms
Antineoplastic Agents / chemistry,  pharmacology
Antioxidants / chemistry,  pharmacology
Apoptosis / drug effects*
Breast Neoplasms / pathology,  physiopathology
Cell Cycle / drug effects
Cell Line, Tumor
Cell Proliferation / drug effects
Colonic Neoplasms / pathology,  physiopathology
Dose-Response Relationship, Drug
Flavones / chemistry,  pharmacology*
G1 Phase / drug effects*
HT29 Cells
Molecular Structure
Time Factors
Reg. No./Substance:
0/Antineoplastic Agents; 0/Antioxidants; 0/Flavones; 478-01-3/nobiletin; 481-53-8/tangeretin

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