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 microM 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.
Matzno
Sumio
S
School of Pharmacy and Pharmaceutical Sciences, Mukogawa Women's University, Nishinomiya, Hyogo, Japan. smatzno@mukogawa-u.ac.jp
Yamaguchi
Yuka
Y
Akiyoshi
Takeshi
T
Nakabayashi
Toshikatsu
T
Matsuyama
Kenji
K
D000970:Antineoplastic Agents / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D016213:Cyclins / Q000032:analysis / Q000096:biosynthesis; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005047:Etoposide / Q000494:pharmacology; D005434:Flow Cytometry; D016195:G2 Phase / Q000187:drug effects; D006801:Humans; D007202:Indicators and Reagents; D008113:Liver Neoplasms / Q000188:drug therapy / Q000473:pathology; D059005:Topoisomerase II Inhibitors; D024483:Vitamin K 3 / Q000494:pharmacology*
D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D016213:Cyclins; D004791:Enzyme Inhibitors; D007202:Indicators and Reagents; D059005:Topoisomerase II Inhibitors; D005047:Etoposide; D024483:Vitamin K 3