title: Betulinic acid induces Bax/Bak-independent cytochrome c release in human nasopharyngeal carcinoma cells.
abstract: Betulinic acid (BetA) is an effective and potential anticancer chemical derived from plants. BetA can kill a broad range of tumor cell lines, but has no effect on untransformed cells. The chemical also kills melanoma, leukemia, lung, colon, breast, prostate and ovarian cancer cells via induction of apoptosis, which depends on caspase activation. However, no reports are yet available about the effects of BetA on nasopharyngeal carcinoma (NPC), a widely spread malignancy in the world, especially in East Asia. In this study, we first showed that BetA can effectively kill CNE2 cells, a cell line derived from NPC. BetA-induced CNE2 apoptosis was characterized by typical apoptosis hallmarks: caspase activation, DNA fragmentation, and cytochrome c release. Overexpression of Bcl-2 and Bcl-xL could partially prevent apoptosis caused by BetA. Moreover, Bax was not activated during the induction of apoptosis. Bax/Bak knockdown and wild-type CNE2 cells showed the same kinetics of cytochrome c release. We then showed that BetA may impair mitochondrial permeability transition pores (mPTPs), which may partially contribute to cytochrome c release. These observations suggest that BetA may serve as a potent and effective anticancer agent in NPC treatment. Further exploration of the mechanism of action of BetA could yield novel breakthroughs in anti-cancer drug discovery.
authors.affiliation: E.N.T Department, The Second Affiliated Hospital of Chongqing Medical University, Chongqing City 400000, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.forename: Wenlong
authors.initials: W
authors.lastname: Luo
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002277:Carcinoma; D020169:Caspases / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D045304:Cytochromes c / Q000378:metabolism*; D053938:DNA Fragmentation / Q000187:drug effects; D006801:Humans; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism; D000083162:Mitochondrial Permeability Transition Pore; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D053978:Pentacyclic Triterpenes; D014315:Triterpenes / Q000494:pharmacology*; D050998:bcl-2 Homologous Antagonist-Killer Protein / Q000378:metabolism*; D051028:bcl-2-Associated X Protein / Q000378:metabolism*; D000094062:Betulinic Acid
chemical_list: D000972:Antineoplastic Agents, Phytogenic; C494772:BAK1 protein, human; C494826:BAX protein, human; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D053978:Pentacyclic Triterpenes; D014315:Triterpenes; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein; D045304:Cytochromes c; D020169:Caspases; D000094062:Betulinic Acid