Tags

Type your tag names separated by a space and hit enter

Effects of trichostatin A, a histone deacetylase inhibitor, on the regulation of apoptosis in H-ras-transformed breast epithelial cells.
Int J Mol Med. 2008 Nov; 22(5):605-11.IJ

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.

Authors+Show Affiliations

College of Pharmacy, Pusan National University, San 30, Geumjeung-gu, Busan 609-735, Korea.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

18949380

Citation

Park, Hyeyoung, et al. "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, vol. 22, no. 5, 2008, pp. 605-11.
Park H, Lee YJ, Kim TH, et al. Effects of trichostatin A, a histone deacetylase inhibitor, on the regulation of apoptosis in H-ras-transformed breast epithelial cells. Int J Mol Med. 2008;22(5):605-11.
Park, H., Lee, Y. J., Kim, T. H., Lee, J., Yoon, S., Choi, W. S., Myung, C. 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(5), 605-11.
Park H, et al. Effects of Trichostatin A, a Histone Deacetylase Inhibitor, On the Regulation of Apoptosis in H-ras-transformed Breast Epithelial Cells. Int J Mol Med. 2008;22(5):605-11. PubMed PMID: 18949380.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of trichostatin A, a histone deacetylase inhibitor, on the regulation of apoptosis in H-ras-transformed breast epithelial cells. AU - Park,Hyeyoung, AU - Lee,Young Jun, AU - Kim,Tae Hyung, AU - Lee,Jaewon, AU - Yoon,Sungpil, AU - Choi,Wahn Soo, AU - Myung,Chang-Seon, AU - Kim,Hyung Sik, PY - 2008/10/25/pubmed PY - 2009/2/4/medline PY - 2008/10/25/entrez SP - 605 EP - 11 JF - International journal of molecular medicine JO - Int J Mol Med VL - 22 IS - 5 N2 - 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. SN - 1107-3756 UR - https://www.unboundmedicine.com/medline/citation/18949380/Effects_of_trichostatin_A_a_histone_deacetylase_inhibitor_on_the_regulation_of_apoptosis_in_H_ras_transformed_breast_epithelial_cells_ L2 - http://www.spandidos-publications.com/ijmm/22/5/605 DB - PRIME DP - Unbound Medicine ER -