title: Relationship between triterpenoid anticancer drug resistance, autophagy, and caspase-1 in adult T-cell leukemia.
abstract: We previously reported that the inflammasome inhibitor cucurbitacin D (CuD) induces apoptosis in human leukemia cell lines. Here, we investigated the effects of CuD and a B-cell lymphoma extra-large (Bcl-xL) inhibitor on autophagy in peripheral blood lymphocytes (PBL) isolated from adult T-cell leukemia (ATL) patients. CuD induced PBL cell death in patients but not in healthy donors. This effect was not significantly inhibited by treatment with rapamycin or 3-methyladenine (3-MA). The Bcl-xL inhibitor Z36 induced death in primary cells from ATL patients including that induced by CuD treatment, effects that were partly inhibited by 3-MA. Similarly, cell death induced by the steroid prednisolone was enhanced in the presence of Z36. A western blot analysis revealed that Z36 also promoted CuD-induced poly(ADP ribose) polymerase cleavage. Interestingly, the effects of CuD and Z36 were attenuated in primary ATL patient cells obtained upon recurrence after umbilical cord blood transplantation, as compared to those obtained before chemotherapy. Furthermore, cells from this patient expressed a high level of caspase-1, and treatment with caspase-1 inhibitor-enhanced CuD-induced cell death. Taken together, these results suggest that rescue from resistance to steroid drugs can enhance chemotherapy, and that caspase-1 is a good marker for drug resistance in ATL patients.
authors.affiliation: Department of Immunology and Parasitology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.|Department of Hematology, University of Occupational and Environmental Health, Kitakyushu, Japan.
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Nakanishi
authors.affiliation: Department of Immunology and Parasitology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.|Department of Clinical Laboratory, Fourth Hospital of Hebei Medical University, Shijiazhuang, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Song
authors.affiliation: Department of Immunology and Parasitology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
authors.forename: Cuiying
authors.initials: C
authors.lastname: He
authors.affiliation: Department of Immunology and Parasitology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
authors.forename: Duo
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of Immunology and Parasitology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Morita
authors.affiliation: Department of Hematology, University of Occupational and Environmental Health, Kitakyushu, Japan.
authors.forename: Junichi
authors.initials: J
authors.lastname: Tsukada
authors.affiliation: Department of Immunology and Parasitology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
authors.forename: Tamotsu
authors.initials: T
authors.lastname: Kanazawa
authors.affiliation: Department of Immunology and Parasitology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Yoshida
keywords: ATL; Apoptosis; Autophagy; Caspase-1; Cucurbitacin D