Effects of trichostatin A, a histone deacetylase inhibitor, on the regulation of apoptosis in H-ras-transformed breast epithelial cells

  • Authors:
    • Hyeyoung Park
    • Young Jun Lee
    • Tae Hyung Kim
    • Jaewon Lee
    • Sungpil Yoon
    • Wahn Soo Choi
    • Chang-Seon Myung
    • Hyung Sik Kim
  • View Affiliations

  • Published online on: November 1, 2008     https://doi.org/10.3892/ijmm_00000062
  • Pages: 605-611
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Abstract

This study examined the mechanism for the anti-cancer effects of histone deacetylase (HDAC) inhibitor trichostatin A (TsA) in H-ras-transformed human breast epithelial (MCF10A-ras) cells. The effects of TsA on anti-cancer effects of MCF10A-ras cells were determined by measuring the level of cell cycle regulator expression and apoptotic cell death using Western blotting and flow cytometry analysis, respectively. TsA induced morphological changes, apoptotic cell death and modulation of the cell cycle regulatory proteins in the MCF10A-ras cells. TsA increased the levels of acetylated histone H3 and H4 in MCF10A-ras cells. In addition, TsA markedly down-regulated the expression of cyclin D1 and CDK4, up-regulated the expression of p21WAF1 and p53 and induced cell cycle arrest at the G1 phase in MCF10A-ras cells. The levels of hyperphosphorylation of the Rb protein were lower in MCF10A-ras cells after the TsA treatment. Furthermore, the up-regulation of p53 promoted Bax expression, which led to the activation of pro-caspase-3 and eventually to apoptosis in MCF10A-ras cells. TsA significantly increased the levels of ERK1/2 phosphorylation in MCF10A-ras cells. Overall, the TsA-activated ERK pathway plays an important role in cell cycle arrest and apoptosis through the ERK-dependent induction of p21 in Ras-related human cancer cells.

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November 2008
Volume 22 Issue 5

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

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Spandidos Publications style
Park H, Lee YJ, Kim TH, Lee J, Yoon S, Choi WS, Myung C and Kim HS: Effects of trichostatin A, a histone deacetylase inhibitor, on the regulation of apoptosis in H-ras-transformed breast epithelial cells. Int J Mol Med 22: 605-611, 2008
APA
Park, H., Lee, Y.J., Kim, T.H., Lee, J., Yoon, S., Choi, W.S. ... Kim, H.S. (2008). Effects of trichostatin A, a histone deacetylase inhibitor, on the regulation of apoptosis in H-ras-transformed breast epithelial cells. International Journal of Molecular Medicine, 22, 605-611. https://doi.org/10.3892/ijmm_00000062
MLA
Park, H., Lee, Y. J., Kim, T. H., Lee, J., Yoon, S., Choi, W. S., Myung, C., Kim, H. S."Effects of trichostatin A, a histone deacetylase inhibitor, on the regulation of apoptosis in H-ras-transformed breast epithelial cells". International Journal of Molecular Medicine 22.5 (2008): 605-611.
Chicago
Park, H., Lee, Y. J., Kim, T. H., Lee, J., Yoon, S., Choi, W. S., Myung, C., Kim, H. S."Effects of trichostatin A, a histone deacetylase inhibitor, on the regulation of apoptosis in H-ras-transformed breast epithelial cells". International Journal of Molecular Medicine 22, no. 5 (2008): 605-611. https://doi.org/10.3892/ijmm_00000062