Antitumor Effect of CGP41251, a New Selective Protein Kinase C Inhibitor, on Human Non-Small Cell Lung Cancer Cells

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The antitumor effect of CGP41251 (4-<I>N</I>-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 1.0μM inhibited the proliferation of these tumor cell lines significantly; However, at 0.1μM, it did not show any significant inhibition. Cell cycle analysis indicated that CGP41251 at 0.5 or 1.0μM arrested the cell cycle progression at the G<SUB>2</SUB>/M phase up to 24 hr, but 0.1μM did not. It seems that the antiproliferative action of CGP41251 against human NSCLC is related to G<SUB>2</SUB>/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.
社団法人日本薬理学会の論文
1996-01-01

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