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

  • Authors:
    • Ji Heon Noh
    • Jae Hwi Song
    • Jung Woo Eun
    • Jeong Kyu Kim
    • Kwang Hwa Jung
    • Hyun Jin Bae
    • Hong Jian Xie
    • Jae Chun Ryu
    • Young Min Ahn
    • Seong Jun Wee
    • Won Sang Park
    • Jung Young Lee
    • Suk Woo Nam
  • View Affiliations

  • Published online on: August 1, 2009     https://doi.org/10.3892/ijmm_00000224
  • Pages: 205-226
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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.

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August 2009
Volume 24 Issue 2

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Noh JH, Song JH, Eun JW, Kim JK, Jung KH, Bae HJ, Xie HJ, Ryu JC, Ahn YM, Wee SJ, Wee SJ, et al: Systemic cell-cycle suppression by Apicidin, a histone deacetylase inhibitor, in MDA-MB-435 cells. Int J Mol Med 24: 205-226, 2009.
APA
Noh, J.H., Song, J.H., Eun, J.W., Kim, J.K., Jung, K.H., Bae, H.J. ... Nam, S.W. (2009). Systemic cell-cycle suppression by Apicidin, a histone deacetylase inhibitor, in MDA-MB-435 cells. International Journal of Molecular Medicine, 24, 205-226. https://doi.org/10.3892/ijmm_00000224
MLA
Noh, J. H., Song, J. H., Eun, J. W., Kim, J. K., Jung, K. H., Bae, H. J., Xie, H. J., Ryu, J. C., Ahn, Y. M., Wee, S. J., Park, W. S., Lee, J. Y., Nam, S. W."Systemic cell-cycle suppression by Apicidin, a histone deacetylase inhibitor, in MDA-MB-435 cells". International Journal of Molecular Medicine 24.2 (2009): 205-226.
Chicago
Noh, J. H., Song, J. H., Eun, J. W., Kim, J. K., Jung, K. H., Bae, H. J., Xie, H. J., Ryu, J. C., Ahn, Y. M., Wee, S. J., Park, W. S., Lee, J. Y., Nam, S. W."Systemic cell-cycle suppression by Apicidin, a histone deacetylase inhibitor, in MDA-MB-435 cells". International Journal of Molecular Medicine 24, no. 2 (2009): 205-226. https://doi.org/10.3892/ijmm_00000224