A thioalkyl derivative of vitamin k inhibits protein tyrosine phosphatases and the expression of both proliferating cell nuclear antigen (PCNA) and cyclin b in hepatoma cells

J. Markovits, T. P. Sun, F. T. Ou, B. I. Carr, F. Y H Wu

Research output: Contribution to journalArticle

Abstract

Compounds of the K vitamin family have recently been shown to have growth inhibitory activity in vitro. VK3 inhibits the growth of human tumor cells by decreasing the activities of both p34clk2 kinase and protein tyrosine phosphatases (PTPases) and may be the first anticancer drug in clinical trial that acts as a PTPase inhibitor. Several novel analogs of vitamin K have recently been synthesized, that are much more potent than the natural vitamins Kl and K2 (J. Biol. Chem. , 1995, 270: 28, 304). These thioalkyl congeners of vitamin K are a novel class of growth inhibitors thai have an unexplored mechanism, although vitamin K acts as a cofactor for gamma-glutamyl carboxylation. We have begun to study the effects of these thioalkyl derivatives of vitamin K on cell cycle related events in HepG2 cells using the most potent analog, cpd 5. Our data show that: (1) cpd 5 is a powerful inhibitor of PTPase IB in vitro, (2) cpd 5 (50 u,M) totally suppressed the expression of cyclin B and partly suppressed the expression of the S-phase specific proliferating cell nuclear antigen (PCNA), These results suggest that cell growth inhibition by cpd 5 may be related to inactivation of PTPases. Judith Markovits is a Visiting Professor from Unite de Biochimie-Enzyrnologie, URA 147 CNRS, Institut Gustave Roussy, 94805 Villejuif, France.

Original languageEnglish
Pages (from-to)752
Number of pages1
JournalExperimental Hematology
Volume25
Issue number8
Publication statusPublished - 1997

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Genetics
  • Hematology
  • Oncology
  • Transplantation

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