title: Induction of mitochondria-dependent apoptosis in HepG2 human hepatocellular carcinoma cells by timosaponin A-III.
abstract: Timosaponin A-III (TSA-III), a saponin isolated from the rhizome of Anemarrhena asphodeloides, exhibits potent cytotoxicity and has the potential to be developed as an anticancer agent. However, the molecular mechanism underlying the anticancer activity of TSA-III has not been fully elucidated. In this study, the apoptotic effects of TSA-III were investigated in HepG2 cells. Treatment with TSA-III significantly inhibited cell growth in a concentration- and time-dependent manner by inducing apoptosis in HepG2 cells. This induction was associated with increased fluorescence intensity of Annexin V-FITC, activation of caspases, and altered expression of inhibitor of apoptosis protein (IAP) family members. In addition, TSA-III mediated mitochondrial dysfunction with the release of HtrA2/Omi, Smac/Diablo, and cytochrome c. These findings suggest that TSA-III induces mitochondria-mediated and caspase-dependent apoptosis in HepG2 cells by altering expression of the IAP family. Thus, TSA-III could possibly be used to treat other types of cancer with similar pathologic mechanisms.
authors.affiliation: K-Herb Research Center, Korea Institute of Oriental Medicine (KIOM), 1672 Yuseong-daero, Yuseong-gu, Daejeon 305-811, Republic of Korea.
authors.forename: Kyoung Jin
authors.initials: KJ
authors.lastname: Nho
authors.affiliation: K-Herb Research Center, Korea Institute of Oriental Medicine (KIOM), 1672 Yuseong-daero, Yuseong-gu, Daejeon 305-811, Republic of Korea.
authors.forename: Jin Mi
authors.initials: JM
authors.lastname: Chun
authors.affiliation: Mibyeong Research Center, KIOM, 1672 Yuseong-daero, Yuseong-gu, Daejeon, 305-811, Republic of Korea. Electronic address: hkkim@kiom.re.kr.
authors.forename: Ho Kyoung
authors.initials: HK
authors.lastname: Kim
mesh_terms: D031403:Anemarrhena / Q000737:chemistry; D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis; D006528:Carcinoma, Hepatocellular / Q000473:pathology; D020169:Caspases / Q000378:metabolism; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism; D021381:Protein Transport; D027343:Rhizome / Q000737:chemistry; D012503:Saponins / Q000302:isolation & purification / Q000494:pharmacology*; D013256:Steroids / Q000302:isolation & purification / Q000494:pharmacology*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D051017:Apoptosis Regulatory Proteins; D012503:Saponins; D013256:Steroids; C543146:timosaponin AIII; D045304:Cytochromes c; D020169:Caspases
keywords: Apoptosis; Caspases; Cytochrome c; IAP family proteins; Timosaponin A-III