Research Papers:

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 and Chia-Ron Yang

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Oncotarget. 2015; 6:18590-18601. https://doi.org/10.18632/oncotarget.4068

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Yen-Chia Huang1,*, Fang-I Huang1,*, Samir Mehndiratta2, Ssu-Chia Lai1, Jing-Ping Liou2, Chia-Ron Yang1

1School of Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan

2School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei, Taiwan

*These authors have contributed equally to this work

Correspondence to:

Chia-Ron Yang, e-mail: [email protected]

Keywords: HDAC, tumor microenvironment, angiogenesis, HIF-1α, Hsp90

Received: February 04, 2015     Accepted: May 15, 2015     Published: May 27, 2015


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.

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