A novel action mechanism for MPT0g013, a derivative of arylsulfonamide, inhibits tumor angiogenesis through upregulation of TIMP3 expression

Chih-Ya Wang, Jing Ping Liou, An-Chi Tsai, Mei-Jung Lai, Yi-Min Liu, Hsueh Yun Lee, Jing-Chi Wang, Shiow Lin Pan, Che-Ming Teng

研究成果: 雜誌貢獻文章

7 引文 (Scopus)

摘要

Tissue inhibitors of metalloproteinases 3 (TIMP3) were originally characterized as inhibitors of matrix metalloproteinases (MMPs), acting as potent antiangiogenic proteins. In this study, we demonstrated that the arylsulfonamide derivative MPT0G013 has potent antiangiogenic activities in vitro and in vivo via inducing TIMP3 expression. Treatments with MPT0G013 significantly inhibited endothelial cell functions, such as cell proliferation, migration, and tube formation, as well as induced p21 and cell cycle arrest at the G0/G1 phase. Subsequent microarray analysis showed significant induction of TIMP3 gene expression by MPT0G013, and siRNA-mediated blockage of TIMP3 up-regulation abrogated the antiangiogenic activities of MPT0G013 and prevented inhibition of p-AKT and p-ERK proteins. Importantly, MPT0G013 exhibited antiangiogenic activities in in vivo Matrigel plug assays, inhibited tumor growth and up-regulated TIMP3 and p21 proteins in HCT116 mouse xenograft models. These data suggest potential therapeutic application of MPT0G013 for angiogenesisrelated diseases such as cancer.
原文英語
頁(從 - 到)9838-9850
頁數13
期刊Oncotarget
5
發行號20
出版狀態已發佈 - 2014

指紋

Tissue Inhibitor of Metalloproteinase-3
Up-Regulation
Neoplasms
Cell Cycle Resting Phase
Proteins
Matrix Metalloproteinase Inhibitors
G1 Phase
Microarray Analysis
Cell Cycle Checkpoints
Heterografts
Small Interfering RNA
Cell Movement
3-(1-(3,4-dimethoxybenzenesulfonyl)-1H-indol-5-yl)-N-hydroxyacrylamide
Endothelial Cells
Cell Proliferation
Gene Expression
Growth

ASJC Scopus subject areas

  • Oncology

引用此文

A novel action mechanism for MPT0g013, a derivative of arylsulfonamide, inhibits tumor angiogenesis through upregulation of TIMP3 expression. / Wang, Chih-Ya; Liou, Jing Ping; Tsai, An-Chi; Lai, Mei-Jung; Liu, Yi-Min; Lee, Hsueh Yun; Wang, Jing-Chi; Pan, Shiow Lin; Teng, Che-Ming.

於: Oncotarget, 卷 5, 編號 20, 2014, p. 9838-9850.

研究成果: 雜誌貢獻文章

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abstract = "Tissue inhibitors of metalloproteinases 3 (TIMP3) were originally characterized as inhibitors of matrix metalloproteinases (MMPs), acting as potent antiangiogenic proteins. In this study, we demonstrated that the arylsulfonamide derivative MPT0G013 has potent antiangiogenic activities in vitro and in vivo via inducing TIMP3 expression. Treatments with MPT0G013 significantly inhibited endothelial cell functions, such as cell proliferation, migration, and tube formation, as well as induced p21 and cell cycle arrest at the G0/G1 phase. Subsequent microarray analysis showed significant induction of TIMP3 gene expression by MPT0G013, and siRNA-mediated blockage of TIMP3 up-regulation abrogated the antiangiogenic activities of MPT0G013 and prevented inhibition of p-AKT and p-ERK proteins. Importantly, MPT0G013 exhibited antiangiogenic activities in in vivo Matrigel plug assays, inhibited tumor growth and up-regulated TIMP3 and p21 proteins in HCT116 mouse xenograft models. These data suggest potential therapeutic application of MPT0G013 for angiogenesisrelated diseases such as cancer.",
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T1 - A novel action mechanism for MPT0g013, a derivative of arylsulfonamide, inhibits tumor angiogenesis through upregulation of TIMP3 expression

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AU - Liou, Jing Ping

AU - Tsai, An-Chi

AU - Lai, Mei-Jung

AU - Liu, Yi-Min

AU - Lee, Hsueh Yun

AU - Wang, Jing-Chi

AU - Pan, Shiow Lin

AU - Teng, Che-Ming

PY - 2014

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N2 - Tissue inhibitors of metalloproteinases 3 (TIMP3) were originally characterized as inhibitors of matrix metalloproteinases (MMPs), acting as potent antiangiogenic proteins. In this study, we demonstrated that the arylsulfonamide derivative MPT0G013 has potent antiangiogenic activities in vitro and in vivo via inducing TIMP3 expression. Treatments with MPT0G013 significantly inhibited endothelial cell functions, such as cell proliferation, migration, and tube formation, as well as induced p21 and cell cycle arrest at the G0/G1 phase. Subsequent microarray analysis showed significant induction of TIMP3 gene expression by MPT0G013, and siRNA-mediated blockage of TIMP3 up-regulation abrogated the antiangiogenic activities of MPT0G013 and prevented inhibition of p-AKT and p-ERK proteins. Importantly, MPT0G013 exhibited antiangiogenic activities in in vivo Matrigel plug assays, inhibited tumor growth and up-regulated TIMP3 and p21 proteins in HCT116 mouse xenograft models. These data suggest potential therapeutic application of MPT0G013 for angiogenesisrelated diseases such as cancer.

AB - Tissue inhibitors of metalloproteinases 3 (TIMP3) were originally characterized as inhibitors of matrix metalloproteinases (MMPs), acting as potent antiangiogenic proteins. In this study, we demonstrated that the arylsulfonamide derivative MPT0G013 has potent antiangiogenic activities in vitro and in vivo via inducing TIMP3 expression. Treatments with MPT0G013 significantly inhibited endothelial cell functions, such as cell proliferation, migration, and tube formation, as well as induced p21 and cell cycle arrest at the G0/G1 phase. Subsequent microarray analysis showed significant induction of TIMP3 gene expression by MPT0G013, and siRNA-mediated blockage of TIMP3 up-regulation abrogated the antiangiogenic activities of MPT0G013 and prevented inhibition of p-AKT and p-ERK proteins. Importantly, MPT0G013 exhibited antiangiogenic activities in in vivo Matrigel plug assays, inhibited tumor growth and up-regulated TIMP3 and p21 proteins in HCT116 mouse xenograft models. These data suggest potential therapeutic application of MPT0G013 for angiogenesisrelated diseases such as cancer.

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