title: Autophagy is associated with cucurbitacin D-induced apoptosis in human T cell leukemia cells.
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.
authors.affiliation: Department of Immunology and Parasitology, University of Occupational and Environmental Health, Japan, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, 807-8555, Japan.
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Nakanishi
authors.affiliation: Department of Immunology and Parasitology, University of Occupational and Environmental Health, Japan, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, 807-8555, Japan.|Department of Clinical Laboratory, Fourth Hospital of Hebei Medical University, No. 169 Tian Shan Street, Shijiazhuang, 050035, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Song
authors.affiliation: Department of Immunology and Parasitology, University of Occupational and Environmental Health, Japan, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, 807-8555, Japan.
authors.forename: Cuiying
authors.initials: C
authors.lastname: He
authors.affiliation: Department of Immunology and Parasitology, University of Occupational and Environmental Health, Japan, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, 807-8555, Japan.
authors.forename: Duo
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of Immunology and Parasitology, University of Occupational and Environmental Health, Japan, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, 807-8555, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Morita
authors.affiliation: Department of Hematology, University of Occupational and Environmental Health, Japan, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, 807-8555, Japan.
authors.forename: Junichi
authors.initials: J
authors.lastname: Tsukada
authors.affiliation: Department of Immunology and Parasitology, University of Occupational and Environmental Health, Japan, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, 807-8555, Japan.
authors.forename: Tamotsu
authors.initials: T
authors.lastname: Kanazawa
authors.affiliation: Department of Immunology and Parasitology, University of Occupational and Environmental Health, Japan, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, 807-8555, Japan. freude@med.uoeh-u.ac.jp.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Yoshida
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects*; D000071186:Beclin-1 / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor / Q000187:drug effects; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000494:pharmacology; D019169:Jurkat Cells / Q000187:drug effects; D015458:Leukemia, T-Cell / Q000188:drug therapy* / Q000473:pathology; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D014315:Triterpenes / Q000008:administration & dosage / Q000494:pharmacology*; D051020:bcl-X Protein / Q000037:antagonists & inhibitors
chemical_list: C543336:5-fluoro-1-(3'-dimethylamino)propyl-indolin-2-one; C494811:BCL2L1 protein, human; C491997:BECN1 protein, human; D000071186:Beclin-1; D007211:Indoles; D014315:Triterpenes; D051020:bcl-X Protein; C025946:3-methyladenine; C038105:cucurbitacin D; D011065:Poly(ADP-ribose) Polymerases; D000225:Adenine
keywords: Adult T cell leukemia; Apoptosis; Autophagy; Cucurbitacin D; Z36