Abstract
Mantle cell lymphoma (MCL), a distinct type of non-Hodgkin lymphoma, is characterised by the overexpression of cyclin D1. Heat shock protein 90 (HSP90) is a molecular chaperon to proteins that regulate cell cycle and survival. 17-allylamino-17-demethoxy-geldanamycin (17-AAG), a HSP90 small molecule inhibitor, induced G(0/1) cell cycle arrest and cell death in a dose- and time-dependent manner in MCL cell lines. This effect was associated with the downregulation of cyclin D1, cdk4 and Akt, depletion of Bid, and activation of the intrinsic/mitochondrial caspase pathway. These data suggest that 17-AAG may have a potential therapeutic value in patients with MCL.
MeSH terms
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Antineoplastic Agents / pharmacology*
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Apoptosis / drug effects
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BH3 Interacting Domain Death Agonist Protein / metabolism
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Benzoquinones / pharmacology*
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Caspase 9
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Caspases / metabolism
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Cell Cycle / drug effects
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Cyclin D1 / metabolism
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Down-Regulation / drug effects
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Drug Evaluation, Preclinical
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Enzyme Activation / drug effects
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Gene Expression Regulation, Neoplastic / drug effects
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HSP90 Heat-Shock Proteins / antagonists & inhibitors*
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Humans
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Lactams, Macrocyclic / pharmacology*
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Lymphoma, Mantle-Cell / genetics
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Lymphoma, Mantle-Cell / metabolism
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Lymphoma, Mantle-Cell / pathology*
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Neoplasm Proteins / genetics
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Neoplasm Proteins / metabolism*
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Proto-Oncogene Proteins c-akt / metabolism
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Tumor Cells, Cultured
Substances
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Antineoplastic Agents
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BH3 Interacting Domain Death Agonist Protein
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BID protein, human
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Benzoquinones
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HSP90 Heat-Shock Proteins
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Lactams, Macrocyclic
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Neoplasm Proteins
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Cyclin D1
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tanespimycin
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Proto-Oncogene Proteins c-akt
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CASP9 protein, human
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Caspase 9
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Caspases