AUY922 effectively targets against activated B cell subtype of diffuse large B-cell lymphoma and low-grade lymphoma cells harboring genetic alteration-associated nuclear factor-B activation
Journal
Leukemia and Lymphoma
Journal Volume
56
Journal Issue
9
Pages
2674-2682
Date Issued
2015
Author(s)
Tsai H.-J.
Shih N.-Y.
Lin H.-Y.
Chen T.-Y.
Chang K.-C.
Lin S.-F.
Chang J.S.
Chen L.-T.
Abstract
Recurrent genetic alterations that are frequently observed in some low-grade lymphomas, such as activated B cell subtype of diffuse large B-cell lymphoma (ABC-DLBCL) and mucosa-associated lymphoid tissue type lymphoma (MALT lymphoma) are usually associated with nuclear factor-B (NF-B) activation and confer resistance to therapy. In this study, we investigated the therapeutic efficacy and molecular mechanisms of AUY922, a novel Hsp90 inhibitor, in representative cell lines OCI-Ly3 (ABC-DLBCL) and MA-1 (a low-grade lymphoma cell line with t(14;18)/IgH-MALT1translocation) to explore its potential use in the treatment of refractory B-cell lymphoma. Our results showed that AUY922 effectively induced growth inhibition and apoptosis of OCI-Ly3 and MA-1 cells, which were accompanied by down-regulation of the expression levels of NF-B and Bcl-2 family proteins, as well as molecules of multiple signaling pathways involving cell proliferation, growth and survival. The growth inhibitory effect of AUY922 was further confirmed in a mouse xenograft model. These findings indicate the potential use of AUY922 in B cell lymphomas. ? 2015 Informa UK, Ltd.
SDGs
Other Subjects
caspase 3; caspase 9; immunoglobulin enhancer binding protein; luminespib; protein bcl 2; 5-(2,4-dihydroxy-5-isopropylphenyl)-4-(4-morpholin-4-ylmethylphenyl)isoxazole-3-carboxylic acid ethylamide; antineoplastic agent; caspase 3; caspase 9; heat shock protein 90; immunoglobulin enhancer binding protein; isoxazole derivative; resorcinol derivative; activated B cell subtype of diffuse large B cell lymphoma; activated B cell subtype of diffuse large B cell lymphoma; animal experiment; animal model; apoptosis; Article; B lymphocyte; cancer inhibition; cell activation; cell cycle arrest; cell growth; cell proliferation; cell survival; controlled study; down regulation; drug efficacy; enzyme activation; growth inhibition; large cell lymphoma; male; marginal zone lymphoma; mouse; nonhuman; priority journal; protein expression; animal; antagonists and inhibitors; B lymphocyte; cancer grading; cell cycle checkpoint; chromosome 14; chromosome 18; chromosome aberration; disease model; drug effects; drug screening; gene translocation; genetics; human; Lymphoma, Large B-Cell, Diffuse; metabolism; mitochondrion; pathology; signal transduction; tumor cell line; tumor volume; Animals; Antineoplastic Agents; Apoptosis; B-Lymphocytes; Caspase 3; Caspase 9; Cell Cycle Checkpoints; Cell Line, Tumor; Cell Proliferation; Cell Survival; Chromosome Aberrations; Chromosomes, Human, Pair 14; Chromosomes, Human, Pair 18; Disease Models, Animal; Down-Regulation; Enzyme Activation; HSP90 Heat-Shock Proteins; Humans; Isoxazoles; Lymphoma, Large B-Cell, Diffuse; Male; Mice; Mitochondria; Neoplasm Grading; NF-kappa B; Resorcinols; Signal Transduction; Translocation, Genetic; Tumor Burden; Xenograft Model Antitumor Assays
Publisher
Taylor and Francis Ltd
Type
journal article