Document Detail


Induction of cell cycle arrest in human MCF-7 breast cancer cells by cis-stilbene derivatives related to VIOXX.
MedLine Citation:
PMID:  19429232     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
In our present study, 12 new cis-stilbene derivatives (CRI-1-CRI-13) related to VIOXX((R)) were synthesized and studied for their inhibitory effects on cell cycle progression and anti-estrogenicity in human adenoma breast cancer MCF-7 cells. Based on the different substituents in the cis-stilbene molecule, we studied a possible structure activity relationship (SAR) for the inhibition of the cell cycle, cytotoxicity and (anti-) estrogenicity. The results showed that some cis-stilbenes have a pronounced effect on cell cycle distribution. CRI-5, 7, 10 and 12 caused an arrest of G2/M phase and reduction of G1/S phase in all tested doses (1-50 microM). In addition, some of these cis-stilbenes, have a moderate anti-estrogenic effect around 10 microM. Based on these results a preliminary SAR for cis-stilbene derivatives is suggested in which the presence and position of methoxy or thiomethoxy groups play an essential role in this cell cycle arrest. For this substitution on the para position of the left aromatic ring appears to be a prerequisite. However, the SAR for anti-estrogenicity appears to be different, but experimental information was too limited to define a possible SAR. In conclusion, our study shows that some synthetic cis-stilbene related to VIOXX might have chemopreventive properties that can effectively interfere with the cell cycle distribution of breast tumor cells.
Authors:
Sunisa Sangjun; Esther de Jong; Sandra Nijmeijer; Thumnoon Mutarapat; Somsak Ruchirawat; Martin van den Berg; Majorie B M van Duursen
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-01-20
Journal Detail:
Title:  Toxicology letters     Volume:  186     ISSN:  0378-4274     ISO Abbreviation:  Toxicol. Lett.     Publication Date:  2009 Apr 
Date Detail:
Created Date:  2009-05-11     Completed Date:  2009-05-29     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7709027     Medline TA:  Toxicol Lett     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  115-22     Citation Subset:  IM    
Affiliation:
Asian Institute of Technology, Mahidol University, Bangkok, Thailand. sunisa@cri.or.th
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MeSH Terms
Descriptor/Qualifier:
Anticarcinogenic Agents / chemical synthesis*,  pharmacology*
Breast Neoplasms / pathology*
Cell Cycle / drug effects*
Cell Line, Tumor
Cell Proliferation / drug effects
Cell Survival / drug effects
Cyclooxygenase 2 Inhibitors / toxicity*
Estrogen Antagonists / chemical synthesis*,  pharmacology*
Female
Flow Cytometry
Humans
Lactones / toxicity*
Stilbenes / chemical synthesis,  toxicity*
Structure-Activity Relationship
Sulfones / toxicity*
Chemical
Reg. No./Substance:
0/Anticarcinogenic Agents; 0/Cyclooxygenase 2 Inhibitors; 0/Estrogen Antagonists; 0/Lactones; 0/Stilbenes; 0/Sulfones; 0/rofecoxib

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