Vitamin K uptake in hepatocytes and hepatoma cells

Life Sci. 2002 Mar 22;70(18):2085-100. doi: 10.1016/s0024-3205(01)01525-9.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Carbon-Carbon Ligases / biosynthesis
  • Carcinoma, Hepatocellular / metabolism*
  • Cell Count
  • Cell Division / drug effects
  • Dose-Response Relationship, Drug
  • Enzyme Induction
  • Focal Nodular Hyperplasia / chemically induced
  • Focal Nodular Hyperplasia / metabolism
  • Focal Nodular Hyperplasia / pathology
  • Growth Inhibitors / pharmacology
  • Hepatocytes / metabolism*
  • Humans
  • Liver Neoplasms / chemically induced
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology
  • Microsomes, Liver / drug effects
  • Microsomes, Liver / enzymology
  • Rats
  • Tumor Cells, Cultured
  • Vitamin K 2 / metabolism*
  • Vitamin K 2 / pharmacology

Substances

  • Growth Inhibitors
  • Vitamin K 2
  • Carbon-Carbon Ligases
  • glutamyl carboxylase