title: Tanshinone IIA induces cytochrome c-mediated caspase cascade apoptosis in A549 human lung cancer cells via the JNK pathway.
abstract: Tanshinone IIA (TSIIA), a natural diterpene quinone in the traditional Chinese medicinal herb Dan-Shen (Salvia miltiorrhiza), has extensively exerted antitumor activity in cellular and animal models. However, the molecular mechanisms underlying the antitumor effects of TSIIA remain largely unknown. The in vitro effects of TSIIA on apoptosis were investigated in A549 non-small cell lung cancer (NSCLC) cells. The data showed that TSIIA significantly suppressed the proliferation of A549 cells in a dose-dependent manner, with IC50 values of 16.0±3.7 and 14.5±3.3 µM at 48 h as determined by Cell Counting Kit-8 (CCK-8) assay and clone formation assay, respectively. The change of mitochondrial morphology and the loss of mitochondrial membrane potential (MMP) were observed during the induction. Furthermore, TSIIA induced A549 cell apoptosis as confirmed by typical morphological changes, with cytochrome c release from the mitochondria and Bax translocation to the mitochondria. Caspase activity data indicated that TSIIA activated caspase-9 and caspase-3 of mitochondria-mediated apoptosis, but not caspase-8 of receptor-mediated apoptosis, which could be largely rescued by SP600125 (JNK inhibitor). Taken together, these findings provide the first evidence that TSIIA inhibits growth of NSCLC A549 cells, induces activation of JNK signaling and triggers caspase cascade apoptosis mediated by the release of cytochrome c, which provides a better understanding of the molecular mechanisms of TSIIA on lung cancer.
authors.affiliation: Department of Thoracic Surgery, The First Affiliated Hospital, Harbin Medical University, Harbin 150001, P.R. China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Thoracic Surgery, The First Affiliated Hospital, Harbin Medical University, Harbin 150001, P.R. China.
authors.forename: Ju
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Thoracic Surgery, The First Affiliated Hospital, Harbin Medical University, Harbin 150001, P.R. China.
authors.forename: Jiu-Yang
authors.initials: JY
authors.lastname: Jiang
authors.affiliation: Department of Cardiovascular Surgery, The First Affiliated Hospital, Harbin Medical University, Harbin 150001, P.R. China.
authors.forename: Shang-Dian
authors.initials: SD
authors.lastname: Liu
authors.affiliation: Department of Thoracic Surgery, The First Affiliated Hospital, Harbin Medical University, Harbin 150001, P.R. China.
authors.forename: Kai
authors.initials: K
authors.lastname: Fu
authors.affiliation: Department of Cardiovascular Surgery, The First Affiliated Hospital, Harbin Medical University, Harbin 150001, P.R. China.
authors.forename: Hong-Yu
authors.initials: HY
authors.lastname: Liu
mesh_terms: D045784:Abietanes / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D015153:Blotting, Western; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism / Q000473:pathology; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000187:drug effects* / Q000502:physiology; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008856:Microscopy, Fluorescence
chemical_list: D045784:Abietanes; D000972:Antineoplastic Agents, Phytogenic; C021751:tanshinone; D045304:Cytochromes c; D020169:Caspases