title: Anticancer activity of MPT0E028, a novel potent histone deacetylase inhibitor, in human colorectal cancer HCT116 cells in vitro and in vivo.
abstract: Recently, histone deacetylase (HDAC) inhibitors have emerged as a promising class of drugs for treatment of cancers, especially subcutaneous T-cell lymphoma. In this study, we demonstrated that MPT0E028, a novel N-hydroxyacrylamide-derived HDAC inhibitor, inhibited human colorectal cancer HCT116 cell growth in vitro and in vivo. The results of NCI-60 screening showed that MPT0E028 inhibited proliferation in both solid and hematological tumor cell lines at micromolar concentrations, and was especially potent in HCT116 cells. MPT0E028 had a stronger apoptotic activity and inhibited HDACs activity more potently than SAHA, the first therapeutic HDAC inhibitor proved by FDA. In vivo murine model, the growth of HCT116 tumor xenograft was delayed and inhibited after treatment with MPT0E028 in a dose-dependent manner. Based on in vivo study, MPT0E028 showed stronger anti-cancer efficacy than SAHA. No significant body weight difference or other adverse effects were observed in both MPT0E028-and SAHA-treated groups. Taken together, our results demonstrate that MPT0E028 has several properties and is potential as a promising anti-cancer therapeutic drug.
authors.affiliation: Pharmacological Institute, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Han-Li
authors.initials: HL
authors.lastname: Huang
authors.forename: Han-Lin
authors.initials: HL
authors.lastname: Huang
authors.forename: Hsueh-Yun
authors.initials: HY
authors.lastname: Lee
authors.forename: An-Chi
authors.initials: AC
authors.lastname: Tsai
authors.forename: Chieh-Yu
authors.initials: CY
authors.lastname: Peng
authors.forename: Mei-Jung
authors.initials: MJ
authors.lastname: Lai
authors.forename: Jing-Chi
authors.initials: JC
authors.lastname: Wang
authors.forename: Shiow-Lin
authors.initials: SL
authors.lastname: Pan
authors.forename: Che-Ming
authors.initials: CM
authors.lastname: Teng
authors.forename: Jing-Ping
authors.initials: JP
authors.lastname: Liou
mesh_terms: D000107:Acetylation / Q000187:drug effects; D020106:Acrylamide / Q000138:chemical synthesis / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000473:pathology*; D005260:Female; D045325:HCT116 Cells; D056572:Histone Deacetylase Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D006877:Hydroxamic Acids / Q000138:chemical synthesis / Q000494:pharmacology*; D007211:Indoles / Q000138:chemical synthesis / Q000494:pharmacology*; D051379:Mice; D014404:Tubulin / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: C577757:3-(1-benzenesulfonyl-2,3-dihydro-1H-indol-5-yl)-N-hydroxyacrylamide; D000970:Antineoplastic Agents; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D007211:Indoles; D014404:Tubulin; D020106:Acrylamide; D006655:Histone Deacetylases