Toosendanin induces apoptosis through suppression of JNK signaling pathway in HL-60 cells.
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.
T10 T11 T12 T13 T14 T15 T16 T17 T18 T19 T1 T20 T2 T3 T4 T5 T6 T7 T8 T9
CHEMICAL CHEMICAL GENE-N GENE-Y GENE-N GENE-Y GENE-Y GENE-Y GENE-Y GENE-N CHEMICAL GENE-N CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL
TSN Toosendanin JNK Bax PARP caspase-3 Bcl-2 CDC42 MEKK1 JNK Toosendanin JNK TSN TSN TSN triterpenoid TSN TSN FITC propidium iodide