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Metabolism of thalidomide by human liver microsome cytochrome CYP2C19 is required for its antimyeloma and antiangiogenic activities in vitro.
MedLine Citation:
PMID:  21638302     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
In this study, we used a system of human liver microsomes to investigate the antimyeloma and antiangiogenic activities of thalidomide. Myeloma cells and human umbilical vein endothelial cells (HUVECs) were treated with thalidomide alone or thalidomide incubated with human liver microsomal protein. We found that thalidomide alone had no direct effect on several multiple myeloma cell lines (U266, NCI-H929, RPMI 8226, LP-1, CZ-1) or on HUVECs in vitro. However, when incubated with human liver microsomal protein, thalidomide (100 µg/ml) caused a decrease of 34.9-46.7% in cell viability in myeloma cells and 12% in HUVECs. Cell cycle analysis and apoptosis detection indicated that the decreases in cell viability were correlated with the induction of apoptosis. Thalidomide incubated with microsomal protein also influenced HUVEC migration and tube formation. These effects were partially reversed by omeprazole (10 µmol/l), a potent inhibitor of CYP2C19, suggesting that CYP2C19 is required for thalidomide to exhibit its antimyeloma and antiangiogenic activities. Copyright © 2011 John Wiley & Sons, Ltd.
Authors:
Yonghua Li; Zujun Jiang; Yang Xiao; Li Li; Yang Gao
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-6-3
Journal Detail:
Title:  Hematological oncology     Volume:  -     ISSN:  1099-1069     ISO Abbreviation:  -     Publication Date:  2011 Jun 
Date Detail:
Created Date:  2011-6-3     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8307268     Medline TA:  Hematol Oncol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2011 John Wiley & Sons, Ltd.
Affiliation:
Department of Hematology, Guangzhou General Hospital of Guangzhou Military Command, Guangzhou, China.
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