title: A248, a novel synthetic HDAC inhibitor, induces apoptosis through the inhibition of specificity protein 1 and its downstream proteins in human prostate cancer cells.
abstract: Histone deacetylase (HDAC) inhibitors are emerging as potent anticancer agents due to their ability to induce apoptosis in various cancer cells, including prostate cancer cells. In the present study, we synthesized a novel HDAC inhibitor, A248, and investigated its apoptotic activity and molecular target in the DU145 and PC3 human prostate cancer cell lines. A248 inhibited the growth of DU145 and PC3 cells and induced apoptosis, as demonstrated by nuclear fragmentation and the accumulation of cells at subG1 phase of cell cycle. The treatment of DU145 and PC3 prostate cancer cells with A248 resulted in the downregulation of specificity protein 1 (Sp1) expression. Since the expression levels of survivin and Mcl-1 depend on Sp1, we also investigated the effects of A248 on survivin and Mcl-1 expression using western blot analysis and immunocytochemistry. The results showed that A248 markedly decreased the expression of survivin and Mcl-1. These data suggest that A248 has apoptotic activity in human prostate cancer cells and that Sp1 may be the molecular target of A248 treatment for inducing apoptosis in prostate cancer cells.
authors.affiliation: Department of Oral Pathology, School of Dentistry and Institute of Oral Bioscience, Brain Korea 21 Project, Chonbuk National University, Jeonju 561-756, Republic of Korea.
authors.forename: Eun-Sun
authors.initials: ES
authors.lastname: Choi
authors.forename: Gyoonhee
authors.initials: G
authors.lastname: Han
authors.forename: Song-Kyu
authors.initials: SK
authors.lastname: Park
authors.forename: Kiho
authors.initials: K
authors.lastname: Lee
authors.forename: Hyun-Jung
authors.initials: HJ
authors.lastname: Kim
authors.forename: Sung-Dae
authors.initials: SD
authors.lastname: Cho
authors.forename: Hwan Mook
authors.initials: HM
authors.lastname: Kim
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology* / Q000633:toxicity; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D008297:Male; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D011471:Prostatic Neoplasms / Q000378:metabolism*; D016329:Sp1 Transcription Factor / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000077022:Survivin
chemical_list: D000970:Antineoplastic Agents; C107489:BIRC5 protein, human; D056572:Histone Deacetylase Inhibitors; D051034:Inhibitor of Apoptosis Proteins; C579095:MCL1 protein, human; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D016329:Sp1 Transcription Factor; D000077022:Survivin