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.
Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.
MeSH terms
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Adult
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Animals
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Antineoplastic Agents / pharmacology
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Apoptosis / drug effects
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Apoptosis Regulatory Proteins / antagonists & inhibitors
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Apoptosis Regulatory Proteins / metabolism
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Biphenyl Compounds / pharmacology
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Biphenyl Compounds / therapeutic use*
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Blotting, Western
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Cell Line
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Cell Line, Tumor
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Cell Survival / drug effects
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Dose-Response Relationship, Drug
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Drug Synergism
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Female
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Human T-lymphotropic virus 1 / drug effects
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Human T-lymphotropic virus 1 / physiology
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Humans
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Immunohistochemistry
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Jurkat Cells
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Leukemia-Lymphoma, Adult T-Cell / drug therapy*
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Leukemia-Lymphoma, Adult T-Cell / metabolism
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Leukemia-Lymphoma, Adult T-Cell / pathology
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Mice
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Mice, SCID
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Nitrophenols / pharmacology
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Nitrophenols / therapeutic use*
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Piperazines / pharmacology
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Piperazines / therapeutic use
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Proto-Oncogene Proteins c-bcl-2 / antagonists & inhibitors
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Proto-Oncogene Proteins c-bcl-2 / metabolism
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Sulfonamides / pharmacology
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Sulfonamides / therapeutic use*
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T-Lymphocytes / drug effects
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T-Lymphocytes / metabolism
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T-Lymphocytes / virology
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Tumor Burden / drug effects
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Xenograft Model Antitumor Assays*
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bcl-X Protein / antagonists & inhibitors
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bcl-X Protein / metabolism
Substances
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ABT-737
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Antineoplastic Agents
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Apoptosis Regulatory Proteins
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BCL2L2 protein, human
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Biphenyl Compounds
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Nitrophenols
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Piperazines
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Proto-Oncogene Proteins c-bcl-2
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Sulfonamides
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bcl-X Protein