Novel oral histone deacetylase inhibitor, MPT0E028, displays potent growth-inhibitory activity against human B-cell lymphoma in vitro and in vivo

Han-Li Huang, Chieh-Yu Peng, Mei-Jung Lai, Chun-Han Chen, Hsueh Yun Lee, Jing-Chi Wang, Jing Ping Liou, Shiow Lin Pan, Che-Ming Teng

研究成果: 雜誌貢獻文章

6 引文 (Scopus)

摘要

Histone deacetylase (HDAC) inhibitor has been a promising therapeutic option in cancer therapy due to its ability to induce growth arrest, differentiation, and apoptosis. In this study, we demonstrated that MPT0E028, a novel HDAC inhibitor, reduces the viability of B-cell lymphomas by inducing apoptosis and shows a more potent HDAC inhibitory effect compared to SAHA, the first HDAC inhibitor approved by the FDA. In addition to HDACs inhibition, MPT0E028 also possesses potent direct Akt targeting ability as measured by the kinome diversity screening assay. Also, MPT0E028 reduces Akt phosphorylation in B-cell lymphoma with an IC50 value lower than SAHA. Transient transfection assay revealed that both targeting HDACs and Akt contribute to the apoptosis induced by MPT0E028, with both mechanisms functioning independently. Microarray analysis also shows that MPT0E028 may regulate many oncogenes expression (e.g., TP53, MYC, STAT family). Furthermore, in vivo animal model experiments demonstrated that MPT0E028 (50-200 mg/kg, po, qd) prolongs the survival rate of mice bearing human B-cell lymphoma Ramos cells and inhibits tumor growth in BJAB xenograft model. In summary, MPT0E028 possesses strong in vitro and in vivo activity against malignant cells, representing a potential therapeutic approach for cancer therapy.
原文英語
頁(從 - 到)4976-4991
頁數16
期刊Oncotarget
6
發行號7
出版狀態已發佈 - 2015

指紋

Histone Deacetylase Inhibitors
B-Cell Lymphoma
Human Activities
Growth
Apoptosis
Neoplasms
Histone Deacetylases
Therapeutics
Microarray Analysis
In Vitro Techniques
3-(1-benzenesulfonyl-2,3-dihydro-1H-indol-5-yl)-N-hydroxyacrylamide
Oncogenes
Heterografts
Inhibitory Concentration 50
Transfection
Animal Models
Phosphorylation

Keywords

  • Akt
  • Apoptosis
  • B-cell lymphoma
  • Histone deacetylase (HDAC)
  • MPT0E028

ASJC Scopus subject areas

  • Oncology

引用此文

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title = "Novel oral histone deacetylase inhibitor, MPT0E028, displays potent growth-inhibitory activity against human B-cell lymphoma in vitro and in vivo",
abstract = "Histone deacetylase (HDAC) inhibitor has been a promising therapeutic option in cancer therapy due to its ability to induce growth arrest, differentiation, and apoptosis. In this study, we demonstrated that MPT0E028, a novel HDAC inhibitor, reduces the viability of B-cell lymphomas by inducing apoptosis and shows a more potent HDAC inhibitory effect compared to SAHA, the first HDAC inhibitor approved by the FDA. In addition to HDACs inhibition, MPT0E028 also possesses potent direct Akt targeting ability as measured by the kinome diversity screening assay. Also, MPT0E028 reduces Akt phosphorylation in B-cell lymphoma with an IC50 value lower than SAHA. Transient transfection assay revealed that both targeting HDACs and Akt contribute to the apoptosis induced by MPT0E028, with both mechanisms functioning independently. Microarray analysis also shows that MPT0E028 may regulate many oncogenes expression (e.g., TP53, MYC, STAT family). Furthermore, in vivo animal model experiments demonstrated that MPT0E028 (50-200 mg/kg, po, qd) prolongs the survival rate of mice bearing human B-cell lymphoma Ramos cells and inhibits tumor growth in BJAB xenograft model. In summary, MPT0E028 possesses strong in vitro and in vivo activity against malignant cells, representing a potential therapeutic approach for cancer therapy.",
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author = "Han-Li Huang and Chieh-Yu Peng and Mei-Jung Lai and Chun-Han Chen and Lee, {Hsueh Yun} and Jing-Chi Wang and Liou, {Jing Ping} and Pan, {Shiow Lin} and Che-Ming Teng",
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TY - JOUR

T1 - Novel oral histone deacetylase inhibitor, MPT0E028, displays potent growth-inhibitory activity against human B-cell lymphoma in vitro and in vivo

AU - Huang, Han-Li

AU - Peng, Chieh-Yu

AU - Lai, Mei-Jung

AU - Chen, Chun-Han

AU - Lee, Hsueh Yun

AU - Wang, Jing-Chi

AU - Liou, Jing Ping

AU - Pan, Shiow Lin

AU - Teng, Che-Ming

PY - 2015

Y1 - 2015

N2 - Histone deacetylase (HDAC) inhibitor has been a promising therapeutic option in cancer therapy due to its ability to induce growth arrest, differentiation, and apoptosis. In this study, we demonstrated that MPT0E028, a novel HDAC inhibitor, reduces the viability of B-cell lymphomas by inducing apoptosis and shows a more potent HDAC inhibitory effect compared to SAHA, the first HDAC inhibitor approved by the FDA. In addition to HDACs inhibition, MPT0E028 also possesses potent direct Akt targeting ability as measured by the kinome diversity screening assay. Also, MPT0E028 reduces Akt phosphorylation in B-cell lymphoma with an IC50 value lower than SAHA. Transient transfection assay revealed that both targeting HDACs and Akt contribute to the apoptosis induced by MPT0E028, with both mechanisms functioning independently. Microarray analysis also shows that MPT0E028 may regulate many oncogenes expression (e.g., TP53, MYC, STAT family). Furthermore, in vivo animal model experiments demonstrated that MPT0E028 (50-200 mg/kg, po, qd) prolongs the survival rate of mice bearing human B-cell lymphoma Ramos cells and inhibits tumor growth in BJAB xenograft model. In summary, MPT0E028 possesses strong in vitro and in vivo activity against malignant cells, representing a potential therapeutic approach for cancer therapy.

AB - Histone deacetylase (HDAC) inhibitor has been a promising therapeutic option in cancer therapy due to its ability to induce growth arrest, differentiation, and apoptosis. In this study, we demonstrated that MPT0E028, a novel HDAC inhibitor, reduces the viability of B-cell lymphomas by inducing apoptosis and shows a more potent HDAC inhibitory effect compared to SAHA, the first HDAC inhibitor approved by the FDA. In addition to HDACs inhibition, MPT0E028 also possesses potent direct Akt targeting ability as measured by the kinome diversity screening assay. Also, MPT0E028 reduces Akt phosphorylation in B-cell lymphoma with an IC50 value lower than SAHA. Transient transfection assay revealed that both targeting HDACs and Akt contribute to the apoptosis induced by MPT0E028, with both mechanisms functioning independently. Microarray analysis also shows that MPT0E028 may regulate many oncogenes expression (e.g., TP53, MYC, STAT family). Furthermore, in vivo animal model experiments demonstrated that MPT0E028 (50-200 mg/kg, po, qd) prolongs the survival rate of mice bearing human B-cell lymphoma Ramos cells and inhibits tumor growth in BJAB xenograft model. In summary, MPT0E028 possesses strong in vitro and in vivo activity against malignant cells, representing a potential therapeutic approach for cancer therapy.

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