Involvement of MAP kinases in the cytotoxicity of acyclic nucleoside phosphonates
Language English Country Greece Media print
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
22287737
PII: 32/2/497
Knihovny.cz E-resources
- MeSH
- Adenine analogs & derivatives pharmacology MeSH
- Enzyme Activation drug effects MeSH
- Extracellular Signal-Regulated MAP Kinases antagonists & inhibitors metabolism MeSH
- Guanine analogs & derivatives pharmacology MeSH
- HL-60 Cells MeSH
- Caspase 3 metabolism MeSH
- Humans MeSH
- MAP Kinase Kinase 4 antagonists & inhibitors metabolism MeSH
- MAP Kinase Signaling System drug effects MeSH
- RNA, Messenger biosynthesis genetics MeSH
- p38 Mitogen-Activated Protein Kinases antagonists & inhibitors biosynthesis genetics metabolism MeSH
- Mitogen-Activated Protein Kinases antagonists & inhibitors biosynthesis genetics metabolism MeSH
- Cell Line, Tumor MeSH
- Organophosphorus Compounds pharmacology MeSH
- Antineoplastic Agents pharmacology MeSH
- Proto-Oncogene Proteins c-akt antagonists & inhibitors metabolism MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- 9-((2-phosphonylmethoxy)ethyl)guanine MeSH Browser
- 9-(2-phosphonylmethoxyethyl)-2,6-diaminopurine MeSH Browser
- Adenine MeSH
- Extracellular Signal-Regulated MAP Kinases MeSH
- Guanine MeSH
- Caspase 3 MeSH
- MAP Kinase Kinase 4 MeSH
- RNA, Messenger MeSH
- p38 Mitogen-Activated Protein Kinases MeSH
- Mitogen-Activated Protein Kinases MeSH
- Organophosphorus Compounds MeSH
- Antineoplastic Agents MeSH
- Proto-Oncogene Proteins c-akt MeSH
BACKGROUND: 9-[2-(phosphonomethoxy)ethyl] guanine (PMEG) is a nucleotide analogue with anticancer activity. Here we investigate the role of ERK, p38, JNK and AKT kinases in PMEG-induced apoptosis. MATERIALS AND METHODS: CCRF-CEM and HL-60 leukemia cells were used to assess MAPK mRNA and protein expression in PMEG-treated cells. MAPK activation was measured using phospho-specific antibodies. Apoptosis was evaluated by caspase-3 and PARP cleavage. RESULTS: Up-regulation of p38β, γ and δ mRNA were observed following PMEG treatment of CCRF-CEM cells, however, the total protein expression remained unchanged. Neither PMEG nor its analogue 9-[2-(phosphonomethoxy) ethyl]-2,6-diaminopurine (PMEDAP) induced p38 kinase phosphorylation in CCRF-CEM cells, whereas increased p38 phosphorylation was observed in HL-60 cells. The ERK pathway was also activated by these compounds. Pretreatment of the cells with the p38 inhibitor SB203580 diminished drug-induced apoptosis whereas inhibition of ERK, JNK or AKT pathways did not. [corrected]. CONCLUSION: PMEG- and PMEDAP-induced. [corrected].
Anticancer Res. 2012 Mar;32(3):1117 PubMed
