Vitamin K uptake in hepatocytes and hepatoma cells.
Hepatocellular carcinoma (HCC) or hepatoma cells have impaired ability to perform vitamin K-dependent carboxylation reactions. Vitamin K can also inhibit growth of HCC cells in vitro. Both carboxylation and growth inhibition are vitamin K dose dependent. We used rat hepatocytes, a vitamin K-growth sensitive (MH7777) and a vitamin K-growth resistant (H4IIE) rat hepatoma cell line to examine vitamin K uptake and vitamin K-mediated microsomal carboxylation. We found that vitamin K is taken up by normal rat hepatocytes against a saturable concentration gradient. The relative rates of uptake by rat hepatocytes and the two rat cell lines MH7777 and H4IIE correlated with their sensitivity to vitamin K-mediated cell growth inhibition. Pooled hepatocytes from liver nodules from rats treated with the hepatocarcinogen diethylnitrosamine (DEN) also had a reduced rate of vitamin K uptake. However, using a cell-free system, microsomes from both normal rat hepatocytes and the two rat hepatoma cell lines had a similar ability to support carboxylation mediated by exogenously added vitamin K. The results support the hypothesis that different sensitivity of hepatoma cells to vitamin K may be due to differences in vitamin K uptake and may be unrelated to the actions of vitamin K on carboxylation.
Li
Zhong-Qian
ZQ
Division of Hematology, The Children's Hospital of Philadelphia, USA.
He
Feng-Yun
FY
Stehle
Christine J
CJ
Wang
Ziqiu
Z
Kar
Siddhartha
S
Finn
Frances M
FM
Carr
Brian I
BI
D000818:Animals; D019735:Carbon-Carbon Ligases / Q000096:biosynthesis; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D002452:Cell Count; D002455:Cell Division / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction; D020518:Focal Nodular Hyperplasia / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D006131:Growth Inhibitors / Q000494:pharmacology; D022781:Hepatocytes / Q000378:metabolism*; D006801:Humans; D008113:Liver Neoplasms / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D051381:Rats; D014407:Tumor Cells, Cultured; D024482:Vitamin K 2 / Q000378:metabolism* / Q000494:pharmacology
D006131:Growth Inhibitors; D024482:Vitamin K 2; D019735:Carbon-Carbon Ligases; C020660:glutamyl carboxylase