Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo nam. 2, 166 10 Prague 6, Czech Republic.
Anticancer Res. 2012 Feb;32(2):497-501.
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.
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.
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].
PMEG- and PMEDAP-induced. [corrected].
9-[2-(膦酸甲氧基)乙基]鸟嘌呤（PMEG）是一种具有抗癌活性的核苷酸类似物。在这里，我们研究了 ERK、p38、JNK 和 AKT 激酶在 PMEG 诱导的细胞凋亡中的作用。
使用 CCRF-CEM 和 HL-60 白血病细胞来评估 PMEG 处理细胞中的 MAPK mRNA 和蛋白表达。使用磷酸化特异性抗体测量 MAPK 激活。通过 caspase-3 和 PARP 切割评估细胞凋亡。
在 CCRF-CEM 细胞中用 PMEG 处理后观察到 p38β、γ 和 δ mRNA 的上调，但总蛋白表达保持不变。PMEG 及其类似物 9-[2-(膦酸甲氧基)乙基]-2,6-二氨基嘌呤（PMEDAP）均未诱导 CCRF-CEM 细胞中 p38 激酶磷酸化，而在 HL-60 细胞中观察到 p38 磷酸化增加。这些化合物还激活了 ERK 通路。用 p38 抑制剂 SB203580 预处理细胞可减少药物诱导的细胞凋亡，而抑制 ERK、JNK 或 AKT 通路则没有。
PMEG 和 PMEDAP 诱导的。
