Autophagy is associated with cucurbitacin D-induced apoptosis in human T cell leukemia cells
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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.
KeywordsAutophagy Adult T cell leukemia Apoptosis Cucurbitacin D Z36
Adult T cell leukemia
Light chain 3-II
Poly-ADP ribose polymerase
Peripheral blood lymphocytes
This study was supported in part by a Grant-in-Aid for Scientific Research (B) (No. 24390159) from the Japan Society for the Promotion of Science to Y. Yoshida.
Compliance with ethical standards
Conflict of interest
The authors have no conflicts of interest that they wish to declare.
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