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WK234, a novel bisindolymaleimide derivative, was designed as a protein kinase Cβ (PKCβ) inhibitor. The objective of this study was to evaluate the anti-tumor activity of WK234 in the human chronic myelogenous leukemia (CML) K562 cell line and to investigate possible mechanisms of its action. The results show that WK234 inhibited K562 cell proliferation in a time- and dose-dependent manner. WK234 increased cytochrome C release and caspase-3 cleavage, which indicates that it induced apoptosis via mitochondria- and caspase-mediated pathways. Western blotting showed that PKCβ1, PKCβ2, and their phosphorylation levels were effectively decreased after 2–4 h of WK234 treatment. Meanwhile the phosphorylation status of PKCβ downstream proteins, glycogen synthase kinase 3α/β (GSK3α/β) and extracellular signal-regulated kinase (ERK), were inhibited. WK234 blocked phorbol myristate acetate …