title: Toosendanin induces apoptosis through suppression of JNK signaling pathway in HL-60 cells.
abstract: Toosendanin (TSN), a triterpenoid isolated from Melia toosendan Sieb. et Zucc., has been found to suppress proliferation and induce apoptosis in a variety of human cancer cells. However, the mechanism how TSN induces apoptosis remains poorly understood. In this study, we examined the effects of TSN on the growth, cell cycle arrest, induction of apoptosis and the involved signaling pathway in human promyelocytic leukemia HL-60 cells. Proliferation of HL-60 cells was inhibited in a dose-dependent manner with the IC(50 (48 h)) of 28 ng/mL. The growth inhibition was due primarily to the S phase arrest and cell apoptosis. Cell apoptosis induced by TSN was confirmed by Annexin V-FITC/propidium iodide staining. The increase of the pro-apoptotic protein Bax, cleaved PARP and caspase-3, and the decrease of anti-apoptotic protein Bcl-2 were observed. Western blot analysis indicated that TSN inhibits the CDC42/MEKK1/JNK pathway. Taken together, our study suggested, for the first time, that the pro-apoptotic effects of TSN on HL-60 cells were mediated through JNK signaling pathway.
authors.affiliation: State Key Laboratory of Natural Medicines and Laboratory of Chemical Biology, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Jianming
authors.initials: J
authors.lastname: Ju
authors.forename: Zhichao
authors.initials: Z
authors.lastname: Qi
authors.forename: Xueting
authors.initials: X
authors.lastname: Cai
authors.forename: Peng
authors.initials: P
authors.lastname: Cao
authors.forename: Nan
authors.initials: N
authors.lastname: Liu
authors.forename: Shuzhen
authors.initials: S
authors.lastname: Wang
authors.forename: Yijun
authors.initials: Y
authors.lastname: Chen
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D018922:HL-60 Cells; D006801:Humans; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D048728:MAP Kinase Kinase Kinase 1 / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism; D014315:Triterpenes
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004365:Drugs, Chinese Herbal; D048670:MAP Kinase Kinase 4; D048728:MAP Kinase Kinase Kinase 1; D020764:cdc42 GTP-Binding Protein; C036454:toosendanin; D014315:Triterpenes; C482576:MAP3K1 protein, human