Vitamin K2 suppresses malignancy of HuH7 hepatoma cells via inhibition of connexin 43

The anti-cancer potential of vitamin K2 (VK2) in hepatoma has gained considerable attention but the underlying mechanisms are unclear. Treatment of HuH7 hepatoma cells with VK2 produced a normal liver phenotype. Following treatment of cells with VK2, there was an increase in gap junctional intercellular communication activity, accompanied by up-regulation of connexin 32 (Cx32), dominantly expressed in normal hepatocyte. In contrast, Cx43 expression was inhibited. Moreover, the effect of VK2 on Cx32 was abolished by over-expression of Cx43. Taken together, we propose that the anti-tumor effect of VK2 is at least partly due to a decrease in Cx43 promoter activity.