title: SAHA inhibits the growth of colon tumors by decreasing histone deacetylase and the expression of cyclin D1 and survivin.
abstract: We studied the effects of suberoylanilide hydroxamic acid (SAHA), a histone deacetylase (HDAC) inhibitor, on colon cancer. The expression of HDACs in colorectal cancer specimens and the effects of SAHA on colon cancer cells and tumors of nude mice were assessed. Treatment with SAHA (3 μm) for 72 h induced downregulation of different subtypes of HDAC proteins and also induced acetylation of histone 3 and histone 4. SAHA significantly inhibited the expression of the oncogenic protein c-myc and also increased the expression of the p53 and Rb proteins. The immunohistochemical staining of HDACs, including HDAC1, HDAC2, HDAC3, and HDAC4, was significantly increased in colorectal adenocarcinoma specimens compared to healthy control tissues. In addition, murine studies showed that 100 mg/kg SAHA administered by intraperitoneal injection significantly induced tumor necrosis and inhibited the growth of colon tumors. Immunohistochemistry of the tumor tissues from nude mice revealed that SAHA inhibited the expression of different subtypes of histone deacetylase, the anti-apoptotic proteins cyclin D1, survivin, and also inhibited cell proliferative as determined by Ki67 expression. SAHA inhibited the growth of colon tumors by decreasing histone deacetylases and the expression of cyclin D1 and survivin in nude mice.
authors.affiliation: Department of Pathology, Tungs' Taichung MetroHarbor Hospital, Wuqi Township, Taichung County, Taiwan, Republic of China.
authors.forename: Jong-Shiaw
authors.initials: JS
authors.lastname: Jin
authors.forename: Tang-Yi
authors.initials: TY
authors.lastname: Tsao
authors.forename: Pei-Chang
authors.initials: PC
authors.lastname: Sun
authors.forename: Cheng-Ping
authors.initials: CP
authors.lastname: Yu
authors.forename: Ching
authors.initials: C
authors.lastname: Tzao
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D000818:Animals; D015153:Blotting, Western; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D019938:Cyclin D1 / Q000378:metabolism*; D005260:Female; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006655:Histone Deacetylases / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D007124:Immunoenzyme Techniques; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D012097:Repressor Proteins / Q000378:metabolism*; D000077022:Survivin; D046888:Tissue Array Analysis; D014407:Tumor Cells, Cultured; D000077337:Vorinostat
chemical_list: C117749:Birc5 protein, mouse; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D051034:Inhibitor of Apoptosis Proteins; D012097:Repressor Proteins; D000077022:Survivin; D019938:Cyclin D1; D000077337:Vorinostat; D006655:Histone Deacetylases