Anticancer activity of MPT0G157, a derivative of indolylbenzenesulfonamide, inhibits tumor growth and angiogenesis

Yen Chia Huang, Fang I. Huang, Samir Mehndiratta, Ssu Chia Lai, Jing Ping Liou, Chia Ron Yang

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Histone deacetylases (HDACs) display multifaceted functions by coordinating the interaction of signal pathways with chromatin structure remodeling and the activation of non-histone proteins; these epigenetic regulations play an important role during malignancy progression. HDAC inhibition shows promise as a new strategy for cancer therapy; three HDAC inhibitors have been approved. We previously reported that N-hydroxy-3-{4-[2-(2-methyl-1H-indol-3-yl)-ethylsulfamoyl]-phenyl}-acrylamide (MPT0G157), a novel indole-3-ethylsulfamoylphenylacrylamide compound, demonstrated potent HDAC inhibition and anti-inflammatory effects. In this study, we evaluated its anti-cancer activity in vitro and in vivo. MPT0G157 treatment significantly inhibited different tumor growth at submicromolar concentration and was particularly potent in human colorectal cancer (HCT116) cells. Apoptosis and inhibited HDACs activity induced by MPT0G157 was more potent than that by the marketed drugs PXD101 (Belinostat) and SAHA (Vorinostat). In an in vivo model, MPT0G157 markedly inhibited HCT116 xenograft tumor volume and reduced matrigel-induced angiogenesis. The anti-angiogenetic effect of MPT0G157 was found to increase the hyperacetylation of heat shock protein 90 (Hsp90) and promote hypoxia-inducible factor-1α (HIF-1α) degradation followed by down-regulation of vascular endothelial growth factor (VEGF) expression. Our results demonstrate that MPT0G157 has potential as a new drug candidate for cancer therapy.

Original languageEnglish
Pages (from-to)18590-18601
Number of pages12
JournalOncotarget
Volume6
Issue number21
Publication statusPublished - 2015

Fingerprint

Histone Deacetylases
Growth
Neoplasms
HCT116 Cells
HSP90 Heat-Shock Proteins
Hypoxia-Inducible Factor 1
Chromatin Assembly and Disassembly
MPT0G157
Tumor Burden
Heterografts
Epigenomics
Pharmaceutical Preparations
Vascular Endothelial Growth Factor A
Colorectal Neoplasms
Signal Transduction
Anti-Inflammatory Agents
Down-Regulation
Apoptosis
Therapeutics
Proteins

Keywords

  • Angiogenesis
  • HDAC
  • HIF-1α
  • Hsp90
  • Tumor microenvironment

ASJC Scopus subject areas

  • Oncology

Cite this

Huang, Y. C., Huang, F. I., Mehndiratta, S., Lai, S. C., Liou, J. P., & Yang, C. R. (2015). Anticancer activity of MPT0G157, a derivative of indolylbenzenesulfonamide, inhibits tumor growth and angiogenesis. Oncotarget, 6(21), 18590-18601.

Anticancer activity of MPT0G157, a derivative of indolylbenzenesulfonamide, inhibits tumor growth and angiogenesis. / Huang, Yen Chia; Huang, Fang I.; Mehndiratta, Samir; Lai, Ssu Chia; Liou, Jing Ping; Yang, Chia Ron.

In: Oncotarget, Vol. 6, No. 21, 2015, p. 18590-18601.

Research output: Contribution to journalArticle

Huang, YC, Huang, FI, Mehndiratta, S, Lai, SC, Liou, JP & Yang, CR 2015, 'Anticancer activity of MPT0G157, a derivative of indolylbenzenesulfonamide, inhibits tumor growth and angiogenesis', Oncotarget, vol. 6, no. 21, pp. 18590-18601.
Huang, Yen Chia ; Huang, Fang I. ; Mehndiratta, Samir ; Lai, Ssu Chia ; Liou, Jing Ping ; Yang, Chia Ron. / Anticancer activity of MPT0G157, a derivative of indolylbenzenesulfonamide, inhibits tumor growth and angiogenesis. In: Oncotarget. 2015 ; Vol. 6, No. 21. pp. 18590-18601.
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