Most cited article - PubMed ID 24000324
Combined treatment with low concentrations of decitabine and SAHA causes cell death in leukemic cell lines but not in normal peripheral blood lymphocytes
While p53-dependent apoptosis is triggered by combination of methyltransferase inhibitor decitabine (DAC) and histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) in leukemic cell line CML-T1, reactive oxygen species (ROS) generation as well as survivin and Bcl-2 deregulation participated in DAC + SAHA-induced apoptosis in p53-deficient HL-60 cell line. Moreover, decrease of survivin expression level is accompanied by its delocalization from centromere-related position in mitotic cells suggesting that both antiapoptotic and cell cycle regulation roles of survivin are affected by DAC + SAHA action. Addition of subtoxic concentration of all-trans-retinoic acid (ATRA) increases the efficiency of DAC + SAHA combination on viability, apoptosis induction, and ROS generation in HL-60 cells but has no effect in CML-T1 cell line. Peripheral blood lymphocytes from healthy donors showed no damage induced by DAC + SAHA + ATRA combination. Therefore, combination of ATRA with DAC and SAHA represents promising tool for therapy of leukemic disease with nonfunctional p53 signalization.
- MeSH
- Apoptosis drug effects MeSH
- Azacitidine analogs & derivatives toxicity MeSH
- Decitabine MeSH
- Down-Regulation drug effects MeSH
- HL-60 Cells MeSH
- Inhibitor of Apoptosis Proteins metabolism MeSH
- G2 Phase Cell Cycle Checkpoints drug effects MeSH
- M Phase Cell Cycle Checkpoints drug effects MeSH
- Hydroxamic Acids toxicity MeSH
- Humans MeSH
- Lymphocytes cytology drug effects immunology MeSH
- Cell Line, Tumor MeSH
- Tumor Suppressor Protein p53 deficiency genetics MeSH
- Antimetabolites, Antineoplastic pharmacology MeSH
- Reactive Oxygen Species metabolism MeSH
- Survivin MeSH
- Drug Synergism MeSH
- Tretinoin pharmacology MeSH
- Vorinostat MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Azacitidine MeSH
- BIRC5 protein, human MeSH Browser
- Decitabine MeSH
- Inhibitor of Apoptosis Proteins MeSH
- Hydroxamic Acids MeSH
- Tumor Suppressor Protein p53 MeSH
- Antimetabolites, Antineoplastic MeSH
- Reactive Oxygen Species MeSH
- Survivin MeSH
- Tretinoin MeSH
- Vorinostat MeSH
