KN-93, a membrane-permeant calcium/calmodulin- dependent kinase-selective 
inhibitor, induces apoptosis in some lines of human tumor cells. We investigated 
the effect of KN-93 in the choriocarcinoma cell line, BeWo. BeWo cells were 
treated with various concentrations of KN-93, and changes in cell growth, the 
cell cycle, apoptosis, and related parameters were examined. A WST-1 assay 
showed that BeWo cells were sensitive to the growth inhibitory effect of KN-93. 
Cell cycle analysis indicated that exposure to KN-93 decreased the proportion of 
cells in the S phase and increased the proportion in the G0/G1 phases of the 
cell cycle. Induction of apoptosis was confirmed by Annexin V staining of 
externalized phosphatidylserine, by the loss of mitochondrial transmembrane 
potential, and by antibodies directed against histones from fragmented DNA. This 
induction occurred in conjunction with the altered expression of genes related 
to cell growth, malignant phenotype, and apoptosis. These results suggest that 
KN-93 may serve as a therapeutic agent for the treatment of choriocarcinoma.