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

Research output: Contribution to journalArticle

8 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)9838-9850
Number of pages13
JournalOncotarget
Volume5
Issue number20
Publication statusPublished - 2014

Keywords

  • Angiogenesis
  • MPT0G013
  • Proliferation
  • TIMP3
  • Tumor

ASJC Scopus subject areas

  • Oncology

Fingerprint Dive into the research topics of 'A novel action mechanism for MPT0g013, a derivative of arylsulfonamide, inhibits tumor angiogenesis through upregulation of TIMP3 expression'. Together they form a unique fingerprint.

  • Cite this