Cureus | Inhibition of Iron Uptake Is Responsible for Differential Sensitivity to V-ATPase Inhibitors in Several Cancer Cell Lines
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Research Article

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

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DOI: 10.1371/journal.pone.0011629

License: Straud et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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.


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Scholarly Impact Quotient™ (SIQ™)

Scholarly Impact Quotient™ (SIQ™) is our unique post-publication peer review rating process. SIQ™ assesses article importance and quality by embracing the collective intelligence of the Cureus community-at-large. All registered users are invited to contribute to the SIQ™ of any published article. (Authors cannot rate their own articles.)

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