Journal
MOLECULAR AND CELLULAR BIOCHEMISTRY
Volume 350, Issue 1-2, Pages 71-80Publisher
SPRINGER
DOI: 10.1007/s11010-010-0683-3
Keywords
Decitabine; SAHA; Apoptosis; CML; Peripheral blood lymphocytes
Categories
Funding
- Ministry of Health of the Czech Republic [NS-9374-6]
- Grant Agency of the Czech Republic [301/09/1026]
Ask authors/readers for more resources
Restoration of cellular apoptotic pathways plays a crucial role in cancer therapy strategies. In a broad spectrum of anticancer drugs, epigenetic effectors are in the center of interest mostly because of potential reversibility of their action. Methylation status of the cells is influenced by methyltransferase inhibitor 2-deoxy-5'-azacytidine (decitabine, DAC), but higher concentrations of this agent cause a DNA-damage. In our study, tumor supressor p53-apoptotic pathway was activated in decitabine-induced cell death. Expression of p53-inducible BH3-only apoptotic proteins Puma and Noxa was elevated and large activation of executive caspases was observed. The extent of acetylation in the cell is affected by histonedeacetylase inhibitor suberoylanilide hydroxamic acid (SAHA). Combination of SAHA with decitabine brought synergistic effect on apoptosis triggering in CML-T1 cell line, but apoptosis as well as necrosis occured also in normal peripheral blood lymphocytes. Therefore, promising potential of such combined therapy calls for more detailed investigation of unwanted effects in normal cells.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available