title: Timosaponin AIII mediates caspase activation and induces apoptosis through JNK1/2 pathway in human promyelocytic leukemia cells.
abstract: Timosaponin AIII (TAIII) is a steroidal saponin isolated from Anemarrhena asphodeloides that has been shown to inhibit cell growth and induce apoptosis in cancer. However, the effect of TAIII on acute myeloid leukemia (AML) remains unclear. Here, the molecular mechanism by which TAIII-induced apoptosis affects human AML cells was investigated. The results showed that TAIII significantly inhibited cell proliferation of four AML cell lines (MV4-11, U937, THP-1, and HL-60). Furthermore, TAIII induced apoptosis of HL-60 cells through caspase-3, caspase-8, and caspase-9 activations and PARP cleavage in a dose- and time-dependent manner. Moreover, Western blot analysis also showed that TAIII increased phosphorylation of JNK1/2 and p38 MAPK in a dose-dependent manner. Inhibition of JNK1/2 by specific inhibitors significantly abolished the TAIII-induced activation of the caspase-8. Taken together, our results suggest that TAIII induces HL-60 cell apoptosis through JNK1/2 pathways and could serve as a potential additional chemotherapeutic agent for treating AML.
authors.affiliation: Institute of Medicine, Chung Shan Medical University, 110, Section 1, Chien-Kuo N. Road, Taichung, 40201, Taiwan.
authors.forename: Hsin-Lien
authors.initials: HL
authors.lastname: Huang
authors.forename: Whei-Ling
authors.initials: WL
authors.lastname: Chiang
authors.forename: Pei-Ching
authors.initials: PC
authors.lastname: Hsiao
authors.forename: Ming-Hsien
authors.initials: MH
authors.lastname: Chien
authors.forename: Hui-Yu
authors.initials: HY
authors.lastname: Chen
authors.forename: Wei-Chun
authors.initials: WC
authors.lastname: Weng
authors.forename: Ming-Ju
authors.initials: MJ
authors.lastname: Hsieh
authors.forename: Shun-Fa
authors.initials: SF
authors.lastname: Yang
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000096:biosynthesis* / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D012503:Saponins / Q000008:administration & dosage*; D013256:Steroids / Q000008:administration & dosage*; D048051:p38 Mitogen-Activated Protein Kinases / Q000096:biosynthesis
chemical_list: D012503:Saponins; D013256:Steroids; C543146:timosaponin AIII; D048051:p38 Mitogen-Activated Protein Kinases; D020169:Caspases