RRC ID 61349
Author Nakanishi T, Song Y, He C, Wang D, Morita K, Tsukada J, Kanazawa T, Yoshida Y.
Title Autophagy is associated with cucurbitacin D-induced apoptosis in human T cell leukemia cells.
Journal Med Oncol
Abstract We previously reported that the inflammasome inhibitor cucurbitacin D (CuD) induces apoptosis in human leukemia cell lines. In the present study, we investigated the effects of co-treatment with an additional Bcl-xL inhibitor, Z36. Treatment with Z36 induced cell death in leukemia cell lines, with MT-4 cells exhibiting the lowest sensitivity to Z36. Co-treatment of cells with Z36 and CuD resulted in a greater degree of cell death for Hut78 and Jurkat cells than treatment with CuD alone. In contrast, co-treatment of MT-4 cells with Z36 and CuD had a suppressive effect on cell death. The autophagy inhibitor 3-methyladenine (3-MA) suppressed the growth of leukemia cell lines HuT78, Jurkat, MT-1, and MT-4. CuD-induced cell death was enhanced by 3-MA in Jurkat cells, but inhibited in MT-4 cells. Western blotting results revealed cleavage of poly(ADP ribose) polymerase (PARP), supporting CuD-induced cell death; 3-MA enhanced CuD-Z36-induced PARP cleavage. Taken together, our results indicate that autophagy negatively regulates chemical-induced cell death of leukemia cells, and that controlling autophagy could be beneficial in the development of more effective chemotherapies against leukemia.
Volume 33(4)
Pages 30
Published 2016-4-1
DOI 10.1007/s12032-016-0743-y
PII 10.1007/s12032-016-0743-y
PMID 26913856
MeSH Adenine / analogs & derivatives Adenine / pharmacology Antineoplastic Combined Chemotherapy Protocols / pharmacology Apoptosis / drug effects Autophagy / drug effects* Beclin-1 / genetics Beclin-1 / metabolism Cell Line, Tumor / drug effects Humans Indoles / administration & dosage Indoles / pharmacology Jurkat Cells / drug effects Leukemia, T-Cell / drug therapy* Leukemia, T-Cell / pathology Poly(ADP-ribose) Polymerases / metabolism Triterpenes / administration & dosage Triterpenes / pharmacology* bcl-X Protein / antagonists & inhibitors
IF 3.252
Resource
Yeast Jurkat(RCB0806)