An attempt to evaluate the effect of vitamin K3 using as an enhancer of anticancer agents

The possibility of vitamin K-3 (VK3) as an anticancer agent was assessed. VK3 dose-dependently diminished the cell viability (measured as esterase activity) with IC50 of 13.7 mu M and Hill coefficient of 3.1 in Hep G(2) cells. It also decreased the population of S phase and arrested cell cycle in the G(2)/M phase in a dose-dependent manner. G(2)/M arrest was regulated by the increment of cyclin A/cdk1 and cyclin A/cdk2 complex, and contrasting cyclin B/cdk1 complex decrease. Finally, combined application demonstrated that VK3 significantly enhanced the cytotoxicity of etoposide, a G(2) phase-dependent anticancer agent, whereas it reduced the cytotoxic activity of irinotecan, a S phase-dependent agent. These findings suggest that VK3 induces G(2)/M arrest by inhibition of cyclin B/cdk1 complex formation, and is thus useful as an enhancer of G(2) phase-dependent drugs in hepatic cancer chemotherapy.