Document Detail


Cytotoxic effects of tanshinones from Salvia miltiorrhiza on doxorubicin-resistant human liver cancer cells.
MedLine Citation:
PMID:  20455578     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
P-Glycoprotein (Pgp) overexpression and alterations in p53 oncogene expression are known to affect chemotherapeutic efficacy in the treatment of human hepatocellular carcinoma (HCC). The present study has demonstrated the anti-HCC potential of cryptotanshinone (1), dihydrotanshinone (2), tanshinone I (3), and tanshinone IIA (4), the active lipophilic constituents of Salvia miltiorrhiza, using MTT and caspase-3 activity assays and poly(ADP-ribose) polymerase cleavage in HepG2, Hep3B, and PLC/PRF/5 cells. THLE-3, a normal human immortalized liver cell line, was used to demonstrate the selective growth inhibitory effect of 3 for a HCC cell line. Compound 1 suppressed doxorubicin efflux, a process mediated by P-glycoprotein, in a Pgp-overexpressed HepG2 subclone (R-HepG2 cells). Despite its moderate cytostatic and pro-apoptotic effects and minimal influence on doxorubicin efflux, 4 provided the best synergism with doxorubicin as determined by the Combination Index, the Loewe additivity model, and the Bliss independence criterion.
Authors:
Wayne Y W Lee; Chartia C M Cheung; Ken W K Liu; K P Fung; John Wong; Paul B S Lai; John H K Yeung
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of natural products     Volume:  73     ISSN:  1520-6025     ISO Abbreviation:  J. Nat. Prod.     Publication Date:  2010 May 
Date Detail:
Created Date:  2010-05-28     Completed Date:  2010-06-25     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7906882     Medline TA:  J Nat Prod     Country:  United States    
Other Details:
Languages:  eng     Pagination:  854-9     Citation Subset:  IM    
Affiliation:
School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR, People's Republic of China.
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MeSH Terms
Descriptor/Qualifier:
Carcinoma, Hepatocellular / drug therapy*,  pathology
Doxorubicin / pharmacology*
Drug Resistance, Neoplasm / drug effects*
Humans
Models, Biological*
Molecular Structure
P-Glycoprotein / metabolism
Phenanthrenes / chemistry,  isolation & purification*,  pharmacology*
Plants, Medicinal / chemistry*
Salvia miltiorrhiza / chemistry*
Chemical
Reg. No./Substance:
0/P-Glycoprotein; 0/Phenanthrenes; 23214-92-8/Doxorubicin; 568-73-0/tanshinone

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


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