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Autophagy is associated with cucurbitacin D-induced apoptosis in human T cell leukemia cells

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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.

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Abbreviations

3-MA:

3-Methyladenine

ATL:

Adult T cell leukemia

CuD:

Cucurbitacin D

LC3-II:

Light chain 3-II

PARP:

Poly-ADP ribose polymerase

PBLs:

Peripheral blood lymphocytes

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Acknowledgments

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.

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Authors and Affiliations

  1. Department of Immunology and Parasitology, University of Occupational and Environmental Health, Japan, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, 807-8555, Japan

    Tsukasa Nakanishi, Yuan Song, Cuiying He, Duo Wang, Kentaro Morita, Tamotsu Kanazawa & Yasuhiro Yoshida

  2. Department of Hematology, University of Occupational and Environmental Health, Japan, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, 807-8555, Japan

    Junichi Tsukada

  3. Department of Clinical Laboratory, Fourth Hospital of Hebei Medical University, No. 169 Tian Shan Street, Shijiazhuang, 050035, China

    Yuan Song

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  1. Tsukasa Nakanishi
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Correspondence to Yasuhiro Yoshida.

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Nakanishi, T., Song, Y., He, C. et al. Autophagy is associated with cucurbitacin D-induced apoptosis in human T cell leukemia cells. Med Oncol 33, 30 (2016). https://doi.org/10.1007/s12032-016-0743-y

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