The antitumor effect of CGP41251 (4'-N-benzoyl staurosporine), a selective 
protein kinase C (PKC) inhibitor, was examined on two kinds of human non-small 
cell lung cancer (NSCLC) cell lines (adenocarcinoma: A549 and squamous cell 
carcinoma: NCI-H520). CGP41251 at 0.5 or 1.0 microM inhibited the proliferation 
of these tumor cell lines significantly; However, at 0.1 microM, it did not show 
any significant inhibition. Cell cycle analysis indicated that CGP41251 at 0.5 
or 1.0 microM arrested the cell cycle progression at the G2/M phase up to 24 hr, 
but 0.1 microM did not. It seems that the antiproliferative action of CGP41251 
against human NSCLC is related to G2/M accumulation. In NCI-H520, CGP41251 
caused DNA re-replication without mitosis. In a nude mice xenograft, CGP41251 at 
a dose of 200 mg/kg showed antitumor activity against these cell lines. 
Histopathologically, expansion of central necrosis was observed, although no 
destruction of tumor nests was seen by CGP41251 administration. In both tumor 
tissues, the PKC activity of the particulate fraction was significantly 
decreased by CGP41251 treatment. From these results, it is thought that the 
antitumor activity of CGP41251 against human NSCLS is accompanied by the 
decrease of PKC activity in the particulate fraction. Moreover, the G2/M arrest 
of the cell cycle induced by CGP41251 might be important for the growth 
inhibitory action of this compound.