Inhibitory effects of vitamin K3 on DNA polymerase and angiogenesis

Vitamins play essential roles in cellular reactions and maintain human health. Recent studies have revealed that some vitamins including D3, B6 and K2 and their derivatives have an anti-cancer effect. As a mechanism, their inhibitory effect on cancer-related angiogenesis has been demonstrated. Vitamin K2 (menaquinones) has an anti-cancer effect in particular for hepatic cancer and inhibits angiogenesis. In the current study, we demonstrated that sole vitamin K3 (menadione) selectively inhibits the in vitro activity of eukaryotic DNA polymerase γ, which is a mitochondrial DNA polymerase, and suppresses angiogenesis in a rat aortic ring model. The anti-angiogenic effect of vitamin K3 has been shown in angiogenesis models using human umbilical vein endothelial cells (HUVECs) with regard to HUVEC growth, tube formation on reconstituted basement membrane and chemotaxis. These results suggest that vitamin K3 may be a potential anti-cancer agent like vitamin K2.This work was supported by the ‘Academic Frontier’ Project for Private Universities (Kobe-Gakuin University), matching fund subsidy from MEXT, 2006-2010, (K.M., H.Y. and Y.M.) and in part by a grant from the Japanese Ministry of Education, Culture, Sports, Science and Technology (MEXT). K.M. acknowledges a Grant-in-Aid for Young Scientists (B) (No. 18700608) from MEXT. Y.M. also acknowledges a Grant-in-Aid for Young Scientists (A) (No. 19680031) from MEXT, and Grants-in-Aid from the Nakashima Foundation and the Foundation of Oil & Fat Industry, Kaikan, Japan