title: Systemic cell-cycle suppression by Apicidin, a histone deacetylase inhibitor, in MDA-MB-435 cells.
abstract: Histone deacetylase (HDAC) inhibitors are emerging as an exciting new class of potential anti-cancer agents for the treatment of solid and hematological malignancies. However, the best characterized HDAC function concerns the control of gene expression via the regulation of transcription activation or repression. To understand the genome-wide effects of HDAC inhibition on gene regulation, we performed serial gene expression analyses from 0 to 48 h after treating MDA-MB-435, a melanoma-derived highly metastatic tumor cell line, with Apicidin, a HDAC inhibitor. Combined-transcriptomic analysis of large-scale molecular changes induced by Apicidin resulted in the identification of 631 outlier genes that were continuously up- or down-regulated during the 48 h study period. When the 631 outlier genes were mapped to known biological processes, cell-cycle suppression emerged as the function most elicited by Apicidin. In addition comprehensive negative cell-cycle regulation by Apicidin was dissected using gene expression data and validated by Western blot analysis. We suggest the 631 outlier genes as a characteristic molecular signature for Apicidin, and propose concurrent transcriptional suppression of major components of cell-cycle regulatory circuit as potent anti-tumor mechanism of Apicidin. Genetic elements identified during this study also provide the possibility of novel therapeutic interventions in tumor metastasis.
authors: Department of Pathology, College of Medicine and Microdissection Genomics Research Center, The Catholic University of Korea, Seoul, Korea.
authors: Ji Heon
authors: JH
authors: Noh
authors: Jae Hwi
authors: JH
authors: Song
authors: Jung Woo
authors: JW
authors: Eun
authors: Jeong Kyu
authors: JK
authors: Kim
authors: Kwang Hwa
authors: KH
authors: Jung
authors: Hyun Jin
authors: HJ
authors: Bae
authors: Hong Jian
authors: HJ
authors: Xie
authors: Jae Chun
authors: JC
authors: Ryu
authors: Young Min
authors: YM
authors: Ahn
authors: Seong Jun
authors: SJ
authors: Wee
authors: Won Sang
authors: WS
authors: Park
authors: Jung Young
authors: JY
authors: Lee
authors: Suk Woo
authors: SW
authors: Nam
mesh_terms: D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects* / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D020411:Oligonucleotide Array Sequence Analysis; D010456:Peptides, Cyclic / Q000494:pharmacology*; D051900:Smad3 Protein / Q000235:genetics / Q000378:metabolism; D013997:Time Factors
chemical_list: D018797:Cell Cycle Proteins; D056572:Histone Deacetylase Inhibitors; D010456:Peptides, Cyclic; D051900:Smad3 Protein; C102351:apicidin; D006655:Histone Deacetylases