Vitamin K uptake in hepatocytes and hepatoma cells

Zhong Qian Li, Feng Yun He, Christine J. Stehle, Ziqiu Wang, Siddhartha Kar, Frances M. Finn, Brian I. Carr

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)2085-2100
Number of pages16
JournalLife Sciences
Volume70
Issue number18
DOIs
Publication statusPublished - Mar 22 2002

Keywords

  • Carboxylation
  • Growth inhibition
  • K vitamins
  • Menaquinone
  • Transport

ASJC Scopus subject areas

  • Pharmacology

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