title: Tanshinone IIA activates calcium-dependent apoptosis signaling pathway in human hepatoma cells.
abstract: Tanshinone IIA (Tan IIA), a natural product from herb Salvia miltiorrhiza Bunge, has potential anti-tumor activity. The aim of this study was to pinpoint the molecular mechanisms underlying Tan IIA-induced cancer cell apoptosis. Human hepatoma BEL-7402 cells treated with Tan IIA underwent assessment with MTT assay for cell viability, 10-day culture for colony formation, flow cytometry and fluorescence microscopy for apoptosis and cell cycle analysis. Changes in intracellular [Ca(2+)] and mitochondrial membrane potential (∆ψ) reflected the calcium-dependent apoptosis pathway. RT-PCR was used to detect gene expression of Bad and metallothionein 1A (MT 1A). Cytotoxicity of Tan IIA was tested in human amniotic mesenchymal stem cells (HAMCs). Tan IIA exhibited dose-dependent and time-dependent anticancer effects on BEL-7402 cells through apoptosis and G(0)/G(1) arrest. Cells treated with Tan IIA increased their intracellular calcium, decreased their mitochondrial membrane potential and induced Bad and MT 1A mRNA expression. No adverse effects of Tan IIA were found in HAMCs. In conclusion, these results indicate that Tan IIA-induced cancer cell apoptosis acts via activation of calcium-dependent apoptosis signaling pathways and upregulation of MT 1A expression.
authors.affiliation: Department of Pharmacology, Pharmaceutical Institute of Guilin Medical University, 541004 Guilin, China.
authors.forename: Zhi-Kai
authors.initials: ZK
authors.lastname: Dai
authors.forename: Jiang-Ke
authors.initials: JK
authors.lastname: Qin
authors.forename: Jiao-E
authors.initials: JE
authors.lastname: Huang
authors.forename: Yong
authors.initials: Y
authors.lastname: Luo
authors.forename: Qing
authors.initials: Q
authors.lastname: Xu
authors.forename: Hai-Lu
authors.initials: HL
authors.lastname: Zhao
mesh_terms: D045784:Abietanes / Q000494:pharmacology* / Q000633:toxicity; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology* / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D020013:Calcium Signaling / Q000187:drug effects* / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D059630:Mesenchymal Stem Cells / Q000187:drug effects; D008668:Metallothionein / Q000235:genetics; D008856:Microscopy, Fluorescence; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D051025:bcl-Associated Death Protein / Q000235:genetics
chemical_list: D045784:Abietanes; D000972:Antineoplastic Agents, Phytogenic; C494819:BAD protein, human; C530099:MT1A protein, human; D012333:RNA, Messenger; D051025:bcl-Associated Death Protein; C021751:tanshinone; D008668:Metallothionein