title: 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.
abstract: 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.
authors.affiliation: Key Laboratory for Molecular Enzymology and Engineering of the Ministry of Education, College of Life Science, Changchun, Jilin, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Li
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Wang
authors.forename: Xuexun
authors.initials: X
authors.lastname: Fang
authors.forename: Kan
authors.initials: K
authors.lastname: He
authors.forename: Xiaoxi
authors.initials: X
authors.lastname: Guo
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Zhan
authors.forename: Chao
authors.initials: C
authors.lastname: Sun
authors.forename: Ying-Hua
authors.initials: YH
authors.lastname: Jin
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D051023:BH3 Interacting Domain Death Agonist Protein / Q000378:metabolism; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000235:genetics / Q000378:metabolism*; D053453:Caspase 9 / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004789:Enzyme Activation / Q000187:drug effects; D005434:Flow Cytometry; D036145:Ginsenosides / Q000737:chemistry / Q000494:pharmacology*; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D015394:Molecular Structure; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology; D053978:Pentacyclic Triterpenes; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D021381:Protein Transport / Q000187:drug effects; D034622:RNA Interference; D014315:Triterpenes / Q000737:chemistry / Q000494:pharmacology*; D051028:bcl-2-Associated X Protein / Q000378:metabolism*; D000094062:Betulinic Acid
chemical_list: D000972:Antineoplastic Agents, Phytogenic; C494826:BAX protein, human; D051023:BH3 Interacting Domain Death Agonist Protein; C494814:BID protein, human; D036145:Ginsenosides; D053978:Pentacyclic Triterpenes; D014315:Triterpenes; D051028:bcl-2-Associated X Protein; C055305:ginsenoside Rh2; D045304:Cytochromes c; D011065:Poly(ADP-ribose) Polymerases; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D000094062:Betulinic Acid