Taoka T, Tokuda M, Tasaka T, Hatase O, Irino S, Norman A W
Division of Biomedical Sciences, University of California, Riverside 92521.
Biochem Biophys Res Commun. 1990 Aug 16;170(3):1151-6. doi: 10.1016/0006-291x(90)90513-m.
To clarify the role of protein kinase C and protein kinase A in cell proliferation and differentiation, the effects of K252a and its derivatives (K252b, KT5720), which have different inhibitory activity to these protein kinases, on the proliferation and differentiation of HL-60 cells were investigated. The proliferation and DNA synthesis of the HL-60 cells were inhibited by K252a in a dose dependent manner. However, K252b and KT5720 which are more specific inhibitors of protein kinase C or protein kinase A, respectively, had no observable effect on cell proliferation. K252a (40nM) enhanced the differentiation of HL-60 cells induced by 1,25(OH)2D3, retinoic acid and DMSO. K252b and KT5720 did not affect 1,25(OH)2D3-induced differentiation. K252a significantly inhibited the differentiation induced by PMA. These results demonstrate that K252a but not its derivatives can function as an antitumor drug and enhancer of the differentiation induced by various inducers.
为阐明蛋白激酶C和蛋白激酶A在细胞增殖和分化中的作用，研究了对这些蛋白激酶具有不同抑制活性的K252a及其衍生物（K252b、KT5720）对HL-60细胞增殖和分化的影响。K252a以剂量依赖性方式抑制HL-60细胞的增殖和DNA合成。然而，分别作为蛋白激酶C或蛋白激酶A更特异性抑制剂的K252b和KT5720对细胞增殖没有明显影响。K252a（40nM）增强了由1,25(OH)2D3、视黄酸和二甲亚砜诱导的HL-60细胞分化。K252b和KT5720不影响1,25(OH)2D3诱导的分化。K252a显著抑制佛波酯诱导的分化。这些结果表明，K252a而非其衍生物可作为抗肿瘤药物和各种诱导剂诱导分化的增强剂。
