Autophagy is associated with cucurbitacin D-induced apoptosis in human T cell leukemia cells.
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.
['Nakanishi|Tsukasa|T|', 'Song|Yuan|Y|', 'He|Cuiying|C|', 'Wang|Duo|D|', 'Morita|Kentaro|K|', 'Tsukada|Junichi|J|', 'Kanazawa|Tamotsu|T|', 'Yoshida|Yasuhiro|Y|']
D000225:Adenine D000971:Antineoplastic Combined Chemotherapy Protocols D017209:Apoptosis D001343:Autophagy D000071186:Beclin-1 D045744:Cell Line, Tumor D006801:Humans D007211:Indoles D019169:Jurkat Cells D015458:Leukemia, T-Cell D011065:Poly(ADP-ribose) Polymerases D014315:Triterpenes D051020:bcl-X Protein
Autophagy Apoptosis Cucurbitacin D Z36 Adult T cell leukemia