Synergy Effect of Vitamin K3 on Cytotoxicity of Campthotecin in HCT116 Cells

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Vitamin K is a fat-soluble vitamin involved in clotting factors of blood coagulation system. Recently, various studies about bone metabolism and anti-cancer effect in vitamin K have been reported. The aim of this study was to examine the synergy effect of vitamin K3 (MK0) on the cytotoxicity of anticancer drugs with different pharmacological actions such as campthotecin (CPT), cisplatinum (CDDP), Taxol, 5-FU and VP-16. The synergism of MK0 with anti-cancer drugs in HCT116 cells was evaluated by MTT assay and by analysis with the method of Chou and Talalay. The combination of CPT with MK0 revealed a highly synergistic effect in HCT116 cells. A partial synergism was observed in the combination of 5-FU or CDDP with MK0. In contrast, the combination of MK0 with Taxol or VP-16 resulted in antagonism. Further, 24-h exposure of HCT116 cells to 10 μM of MK0 and 10 nM CPT was associated with an increased proportion of cells in S phase, and this combination of drugs promoted arrest in S and/or G2 + M phase, resulting in the enhancement of cytotoxicity of CPT by MK0. In addition, this synergism was taken place at the early phase after the treatment of both drugs by time-lapse microscopic analysis. These findings raised the possibility that the chemotherapy of MK0 with topoisomerase I poison may be useful for the improvement of patients with malignancy in clinic.