Vitamin K2 suppresses malignancy of HuH7 hepatoma cells via inhibition of connexin 43.
The anti-cancer potential of vitamin K(2) (VK(2)) in hepatoma has gained considerable attention but the underlying mechanisms are unclear. Treatment of HuH7 hepatoma cells with VK(2) produced a normal liver phenotype. Following treatment of cells with VK(2), 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 VK(2) on Cx32 was abolished by over-expression of Cx43. Taken together, we propose that the anti-tumor effect of VK(2) is at least partly due to a decrease in Cx43 promoter activity.
Kaneda
Makoto
M
Department of Cellular Physiological Chemistry, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8549, Japan.
Zhang
Dan
D
Bhattacharjee
Rajib
R
Nakahama
Ken-ichi
K
Arii
Shigeki
S
Morita
Ikuo
I
D001483:Base Sequence; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000473:pathology*; D045744:Cell Line, Tumor; D017630:Connexins / Q000037:antagonists & inhibitors* / Q000235:genetics; D017931:DNA Primers; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000235:genetics / Q000473:pathology*; D011401:Promoter Regions, Genetic; D024482:Vitamin K 2 / Q000494:pharmacology*; D000097002:Gap Junction beta-1 Protein
D017630:Connexins; D017931:DNA Primers; D024482:Vitamin K 2; D000097002:Gap Junction beta-1 Protein; C081624:connexin 42