alexa Involvement of MAP kinases in the cytotoxicity of acyclic nucleoside phosphonates.


Journal of Addiction Research & Therapy

Author(s): MertlkovKaiserov H, Nejedl M, Holy A, Votruba I

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Abstract 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].
This article was published in Anticancer Res and referenced in Journal of Addiction Research & Therapy

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