Tumor cell growth inhibition and extracellular signal-regulated kinase (ERK) phosphorylation by novel K vitamins

Shinji Osada, Kazuko Osada, Brian I. Carr

Research output: Contribution to journalArticlepeer-review

Abstract

2-(2-Hydroxy-ethylsulfanyl)-3-methyl-1,4-naphthoquinone or CPD-5, a K vitamin analog, was previously indicated to be a potent growth inhibitor for Hep 3B hepatoma cells in vitro. Here, we show that CPD-5 and two newly synthesized analogs, 2-(2-hydroxy-ethylsulfanyl)-3-methyl-5 nitro-1,4-naphthoquinone (PD-37) and 2-(2-hydroxy-ethylsulfanyl)-3- methyl-5-acetylamino-1,4-naphthoquinone (PD-42), are potent growth inhibitors of 13 different human cancer cell lines, with IC50 values in the range of 3-54 μM. Phospho-ERK was induced by each of three K vitamin analogs in every cell line in a dose-dependent manner, at growth inhibitory doses. ERK phosphorylation and growth inhibitory effects were strongly correlated, with p = 0.0080 for CPD-5, p = 0.0076 for PD-37 and p = 0.0251 for PD-42. The induction of phospho-ERK and growth inhibition were antagonized by thiol-containing anti-oxidants, but not by catalase, consistent with a possible arylating mechanism. The data show a novel class of growth inhibitors with a wide spectrum of action that induces ERK hyper-phosphorylation, as a possible new growth inhibitory feature.

Original languageEnglish
Pages (from-to)765-772
Number of pages8
JournalJournal of Molecular Biology
Volume314
Issue number4
DOIs
Publication statusPublished - Dec 7 2001

Keywords

  • Cancer cell line
  • Extracellular signal-regulated kinase (ERK)
  • Growth inhibition
  • Novel K vitamin analog
  • Phosphorylation

ASJC Scopus subject areas

  • Virology

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