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

Hui Jen Tsai, Neng Yao Shih, Sung Hsin Kuo, Ann Lii Cheng, Hui You Lin, Tsai-Yun Chen, Kung-Chao Chang, Sheng Fung Lin, Jeffrey S. Chang, Li Tzong Chen

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)2674-2682
Number of pages9
JournalLeukemia and Lymphoma
Volume56
Issue number9
DOIs
Publication statusPublished - 2015 Sep 2

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Lymphoma, Large B-Cell, Diffuse
Non-Hodgkin's Lymphoma
B-Lymphocytes
Marginal Zone B-Cell Lymphoma
B-Cell Lymphoma
Growth
Cell Line
Heterografts
Cell Survival
Down-Regulation
Cell Proliferation
Apoptosis
5-(2,4-dihydroxy-5-isopropylphenyl)-4-(4-morpholin-4-ylmethylphenyl)isoxazole-3-carboxylic acid ethylamide
Therapeutics
Proteins
7-hydroxy-6-methoxyphthalide

All Science Journal Classification (ASJC) codes

  • Hematology
  • Oncology
  • Cancer Research

Cite this

Tsai, Hui Jen ; Shih, Neng Yao ; Kuo, Sung Hsin ; Cheng, Ann Lii ; Lin, Hui You ; Chen, Tsai-Yun ; Chang, Kung-Chao ; Lin, Sheng Fung ; Chang, Jeffrey S. ; Chen, Li Tzong. / 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. In: Leukemia and Lymphoma. 2015 ; Vol. 56, No. 9. pp. 2674-2682.
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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.",
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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. / Tsai, Hui Jen; Shih, Neng Yao; Kuo, Sung Hsin; Cheng, Ann Lii; Lin, Hui You; Chen, Tsai-Yun; Chang, Kung-Chao; Lin, Sheng Fung; Chang, Jeffrey S.; Chen, Li Tzong.

In: Leukemia and Lymphoma, Vol. 56, No. 9, 02.09.2015, p. 2674-2682.

Research output: Contribution to journalArticle

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AU - Lin, Hui You

AU - Chen, Tsai-Yun

AU - Chang, Kung-Chao

AU - Lin, Sheng Fung

AU - Chang, Jeffrey S.

AU - Chen, Li Tzong

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