https://scholars.lib.ntu.edu.tw/handle/123456789/565277
標題: | Anticancer activity of MPT0G157, a derivative of indolylbenzenesulfonamide, inhibits tumor growth and angiogenesis | 作者: | Huang Y.-C. Huang F.-I. Mehndiratta S. Lai S.-C. Liou J.-P. CHIA-RON YANG |
關鍵字: | Angiogenesis; HDAC; HIF-1α; Hsp90; Tumor microenvironment | 公開日期: | 2015 | 卷: | 6 | 期: | 21 | 起(迄)頁: | 18590-18601 | 來源出版物: | Oncotarget | 摘要: | 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. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-84938777793&doi=10.18632%2foncotarget.4068&partnerID=40&md5=d1be0ff18a503b7e9506b8db431d8cc8 https://scholars.lib.ntu.edu.tw/handle/123456789/565277 |
ISSN: | 19492553 | DOI: | 10.18632/oncotarget.4068 | SDG/關鍵字: | antineoplastic agent; belinostat; heat shock protein 90; histone deacetylase; hypoxia inducible factor 1alpha; n hydroxy 3 [4 [2 (2 methyl 1h indol 3 yl)ethylsulfamoyl]phenyl]acrylamide; unclassified drug; vasculotropin; vorinostat; antineoplastic agent; HIF1A protein, human; histone deacetylase; histone deacetylase inhibitor; hydroxamic acid; hypoxia inducible factor 1alpha; MPT0G157; sulfonamide; vasculotropin A; animal experiment; animal model; animal tissue; antiangiogenic activity; antineoplastic activity; apoptosis; Article; cancer inhibition; colorectal cancer; concentration response; controlled study; down regulation; drug mechanism; enzyme activity; female; HCT116 cell line; human; human cell; human tissue; in vitro study; in vivo study; male; mouse; nonhuman; protein acetylation; protein degradation; protein expression; tumor volume; tumor xenograft; animal; cell proliferation; chemical structure; chemistry; Colonic Neoplasms; dose response; drug effects; drug screening; gene expression regulation; genetics; HCT 116 cell line; metabolism; Neovascularization, Pathologic; nude mouse; pathology; reverse transcription polymerase chain reaction; tumor cell line; vascularization; Western blotting; Animals; Antineoplastic Agents; Apoptosis; Blotting, Western; Cell Line, Tumor; Cell Proliferation; Colonic Neoplasms; Dose-Response Relationship, Drug; Gene Expression Regulation, Neoplastic; HCT116 Cells; Histone Deacetylase Inhibitors; Histone Deacetylases; Humans; Hydroxamic Acids; Hypoxia-Inducible Factor 1, alpha Subunit; Male; Mice, Nude; Molecular Structure; Neovascularization, Pathologic; Reverse Transcriptase Polymerase Chain Reaction; Sulfonamides; Tumor Burden; Vascular Endothelial Growth Factor A; Xenograft Model Antitumor Assays |
顯示於: | 藥學系 |
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