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

The possibility of vitamin K₃ (VK₃) as an anticancer agent was assessed. VK₃ dose-dependently diminished the cell viability (measured as esterase activity) with IC₅₀ of 13.7 μM and Hill coefficient of 3.1 in Hep G2 cells. It also decreased the population of S phase and arrested cell cycle in the G₂/M phase in a dose-dependent manner. G₂/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 G₂ 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 G₂ phase-dependent drugs in hepatic cancer chemotherapy.