title: Targeting Bcl-2 family proteins in adult T-cell leukemia/lymphoma: in vitro and in vivo effects of the novel Bcl-2 family inhibitor ABT-737.
abstract: Adult T-cell leukemia/lymphoma (ATLL) is a peripheral T-cell malignancy caused by human T-lymphotropic virus type I (HTLV-1). ABT-737, a small molecule inhibitor of Bcl-2, Bcl-X(L), and Bcl-w, significantly induced apoptosis in HTLV-1 infected T-cell lines as well as in fresh ATLL cells, and synergistically enhanced the cytotoxicity and apoptosis induced by conventional cytotoxic drugs. Moreover, ABT-737 significantly inhibited the in vivo tumor growth of an ATLL mouse model. These results suggest that the use of an agent targeting anti-apoptotic bcl-2 family proteins, either alone or in combination with other conventional drugs, represents a novel promising approach for ATLL.
authors.affiliation: Department of Internal Medicine, Division of Medical Oncology, Hematology and Infectious Disease, Fukuoka University, 7-45-1 Nanakuma, Jonan, Fukuoka 814-0180, Japan. kenjiishitsuka@fukuoka-u.ac.jp
authors.forename: Kenji
authors.initials: K
authors.lastname: Ishitsuka
authors.forename: Naoko
authors.initials: N
authors.lastname: Kunami
authors.forename: Hiroo
authors.initials: H
authors.lastname: Katsuya
authors.forename: Rumiko
authors.initials: R
authors.lastname: Nogami
authors.forename: Chie
authors.initials: C
authors.lastname: Ishikawa
authors.forename: Fusanori
authors.initials: F
authors.lastname: Yotsumoto
authors.forename: Hiroe
authors.initials: H
authors.lastname: Tanji
authors.forename: Naoki
authors.initials: N
authors.lastname: Mori
authors.forename: Morishige
authors.initials: M
authors.lastname: Takeshita
authors.forename: Shingo
authors.initials: S
authors.lastname: Miyamoto
authors.forename: Kazuo
authors.initials: K
authors.lastname: Tamura
mesh_terms: D000328:Adult; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D001713:Biphenyl Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D015153:Blotting, Western; D002460:Cell Line; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005260:Female; D015368:Human T-lymphotropic virus 1 / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D019169:Jurkat Cells; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D016513:Mice, SCID; D009596:Nitrophenols / Q000494:pharmacology / Q000627:therapeutic use*; D010879:Piperazines / Q000494:pharmacology / Q000627:therapeutic use; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology / Q000627:therapeutic use*; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism / Q000821:virology; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays; D051020:bcl-X Protein / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: C501332:ABT-737; D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; C491073:BCL2L2 protein, human; D001713:Biphenyl Compounds; D009596:Nitrophenols; D010879:Piperazines; D019253:Proto-Oncogene Proteins c-bcl-2; D013449:Sulfonamides; D051020:bcl-X Protein