Inhibition of iron uptake is responsible for differential sensitivity to V-ATPase inhibitors in several cancer cell lines

Sarah Straud, Iryna Zubovych, Jef K. de Brabander, Michael G. Roth

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

Many cell lines derived from tumors as well as transformed cell lines are far more sensitive to V-ATPase inhibitors than normal counterparts. The molecular mechanisms underlying these differences in sensitivity are not known. Using global gene expression data, we show that the most sensitive responses to HeLa cells to low doses of V-ATPase inhibitors involve genes responsive to decreasing intracellular iron or decreasing cholesterol and that sensitivity to iron uptake is an important determinant of V-ATPase sensitivity in several cancer cell lines. One of the most sensitive cell lines, melanoma derived SK-Mel-5, over-expresses the iron efflux transporter ferroportin and has decreased expression of proteins involved in iron uptake, suggesting that it actively suppresses cytoplasmic iron. SK-Mel-5 cells have increased production of reactive oxygen species and may be seeking to limit additional production of ROS by iron.

Original languageEnglish (US)
Article numbere11629
JournalPloS one
Volume5
Issue number7
DOIs
StatePublished - Jul 16 2010

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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