An Attempt to Evaluate the Effect of Vitamin K3 Using as an Enhancer of Anticancer Agents

• Published in: Biological & Pharmaceutical Bulletin 2008/06/01, Vol.31(6), pp.1270-1273
• Main Authors: Matzno, Sumio, Yamaguchi, Yuka, Akiyoshi, Takeshi, Nakabayashi, Toshikatsu, Matsuyama, Kenji
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents - pharmacology; Antineoplastic Agents, Phytogenic - pharmacology; Cell Cycle - drug effects; Cell Division - drug effects; Cell Line, Tumor; Cell Proliferation - drug effects; Cyclins - analysis; Cyclins - biosynthesis; Drug Synergism; Enzyme Inhibitors - pharmacology; etoposide; Etoposide - pharmacology; Flow Cytometry; G2 Phase - drug effects; G2/M arrest; hepatic cancer; Humans; Indicators and Reagents; Liver Neoplasms - drug therapy; Liver Neoplasms - pathology; Topoisomerase II Inhibitors; Vitamin K 3 - pharmacology; vitamin K3
• ISSN: 0918-6158; 1347-5215
• DOI: 10.1248/bpb.31.1270

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 G2/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.