Co-treatment with ginsenoside Rh2 and betulinic acid synergistically induces apoptosis in human cancer cells in association with enhanced capsase-8 activation, bax translocation, and cytochrome c release.

Li Q, Li Y, Wang X, Fang X, He K, Guo X, Zhan Z, Sun C, Jin YH
Mol Carcinog. 2011 50 (10): 760-9

PMID: 21751259 · DOI:10.1002/mc.20673

We provide evidence for the first time, that two natural compounds ginsenoside Rh2 (G-Rh2) and betulinic acid (Bet A) synergistically induce apoptosis in human cervical adenocarcinoma (HeLa), human lung cancer A549, and human hepatoma HepG2 cells. G-Rh2 and Bet A cooperated to induce Bax traslocation to mitochondria and cytochrome c release. Co-treatment of G-Rh2 and Bet A resulted in enhanced cleavage of caspase-8 and Bid. Moreover, specific inhibition of caspase-8 by siRNA technology effectively reduced caspase-9 processing, poly (ADP-ribose) polymerase (PARP) cleavage, caspase-3 activation, and apoptosis in co-treated cells, which indicated that the caspase-8 feedback amplification pathway may have been involved in the apoptosis process. A previous study has shown that G-Rh2 induces cancer cell apoptosis via a Bcl-2 and/or Bcl-xL-independent mechanism, and Bet A induces apoptosis mainly through a mitochondrial pathway with tumor specificity. Since the antiapoptotic Bcl-2 and Bcl-xL are frequently overexpressed in human cancer cells, combined treatment with G-Rh2 and Bet A may be a novel strategy to enhance efficacy of anticancer therapy. © 2011 Wiley-Liss, Inc.

Copyright © 2011 Wiley-Liss, Inc.

MeSH Terms (25)

Antineoplastic Agents, Phytogenic Apoptosis bcl-2-Associated X Protein BH3 Interacting Domain Death Agonist Protein Blotting, Western Caspase 3 Caspase 8 Caspase 9 Cell Line, Tumor Cell Survival Cytochromes c Dose-Response Relationship, Drug Drug Synergism Enzyme Activation Flow Cytometry Ginsenosides HeLa Cells Hep G2 Cells Humans Molecular Structure Neoplasms Poly(ADP-ribose) Polymerases Protein Transport RNA Interference Triterpenes

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