Cytotoxic effects of tanshinones from Salvia miltiorrhiza on doxorubicin-resistant human liver cancer cells
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AbstractP-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. © 2010 The American Chemical Society and American Society of Pharmacognosy.
All Author(s) ListLee W.Y.W., Cheung C.C.M., Liu K.W.K., Fung K.P., Wong J., Lai P.B.S., Yeung J.H.K.
Journal nameJournal of Natural Products
Year2010
Month5
Day28
Volume Number73
Issue Number5
PublisherAmerican Chemical Society
Place of PublicationUnited States
Pages854 - 859
ISSN0163-3864
eISSN1520-6025
LanguagesEnglish-United Kingdom