Most cited article - PubMed ID 18348176
BimEL-dependent apoptosis induced in peripheral blood lymphocytes with n-butyric acid is moderated by variation in expression of c-myc and p21(WAF1)
Reactive oxygen species play an important role in the process of apoptosis in many cell types. In this paper, we analyzed the role of ROS in DNA-damaging agents (actinomycin D or decitabine), which induced apoptosis of leukemia cell line CML-T1 and normal peripheral blood lymphocytes (PBL). The possibility of synergism with histone deacetylase inhibitors butyrate or SAHA is also reported. We found that in cancer cell line, ROS production significantly contributed to apoptosis triggering, while in normal lymphocytes treated by cytostatic or cytotoxic drugs, necrosis as well as apoptosis occurred and large heterogeneity of ROS production was measured. Combined treatment with histone deacetylase inhibitor did not potentiate actinomycin D action, whereas combination of decitabine and SAHA brought synergistic ROS generation and apoptotic features in CML cell line. Appropriate decrease of cell viability indicated promising therapeutic potential of this combination in CML, but side effects on normal PBL should be taken into attention.
- MeSH
- Apoptosis drug effects MeSH
- Azacitidine analogs & derivatives pharmacology MeSH
- Butyrates pharmacology MeSH
- Cytostatic Agents pharmacology MeSH
- Dactinomycin pharmacology MeSH
- Decitabine MeSH
- Histone Deacetylase Inhibitors pharmacology MeSH
- Caspase 3 metabolism MeSH
- Hydroxamic Acids pharmacology MeSH
- Humans MeSH
- Cell Line, Tumor MeSH
- Poly(ADP-ribose) Polymerases metabolism MeSH
- DNA Damage drug effects MeSH
- Antineoplastic Agents pharmacology MeSH
- Reactive Oxygen Species metabolism MeSH
- Drug Synergism 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
- Butyrates MeSH
- Cytostatic Agents MeSH
- Dactinomycin MeSH
- Decitabine MeSH
- Histone Deacetylase Inhibitors MeSH
- Caspase 3 MeSH
- Hydroxamic Acids MeSH
- Poly(ADP-ribose) Polymerases MeSH
- Antineoplastic Agents MeSH
- Reactive Oxygen Species MeSH
- Vorinostat MeSH