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The heat shock protein 90 inhibitor 17‐AAG induces cell cycle arrest and apoptosis in mantle cell lymphoma cell lines by depleting cyclin D1, Akt, Bid and activating caspase 9
Author(s) -
Georgakis Georgios V.,
Li Yang,
Younes Anas
Publication year - 2006
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.2006.06247.x
Subject(s) - cyclin d1 , geldanamycin , mantle cell lymphoma , protein kinase b , heat shock protein , cell cycle checkpoint , cancer research , cell cycle , hsp90 inhibitor , hsp90 , microbiology and biotechnology , chemistry , apoptosis , cyclin d , cyclin dependent kinase , hsp70 , biology , lymphoma , immunology , biochemistry , gene
Summary 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.