Systemic cell-cycle suppression by Apicidin, a histone deacetylase inhibitor, in MDA-MB-435 cells

Title
Systemic cell-cycle suppression by Apicidin, a histone deacetylase inhibitor, in MDA-MB-435 cells
Authors
노지헌송재희은정우김정규정광화배현진Hong Jian Xie류재천안영민위성준박원상이정용남석우
Keywords
cell-cycle suppression; Apicidin; MDA-MB-435 human melanoma cells; HDAC inhibitor; DNA microarray
Issue Date
2009-08
Publisher
International journal of molecular medicine
Citation
VOL 24, NO 2, 205-226
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 MDAMB- 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.
URI
http://pubs.kist.re.kr/handle/201004/36275
ISSN
1107-3756
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KIST Publication > Article
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