Add like
Add dislike
Add to saved papers

Cell-cell contacts protect against t-BuOOH-induced cellular damage and ferroptosis in vitro.

Archives of Toxicology 2019 Februrary 24
Ferroptosis is a recently discovered pathway of regulated necrosis dependent on iron and lipid peroxidation. It has gained broad attention since it is a promising approach to overcome resistance to apoptosis in cancer chemotherapy. We have recently identified tertiary-butyl hydroperoxide (t-BuOOH) as a novel inducer of ferroptosis. t-BuOOH is a widely used compound to induce oxidative stress in vitro. t-BuOOH induces lipid peroxidation and consequently ferroptosis in murine and human cell lines. t-BuOOH additionally results in a loss of mitochondrial membrane potential, formation of DNA double-strand breaks, and replication block. Here, we specifically address the question whether cell-cell contacts regulate t-BuOOH-induced ferroptosis and cellular damage. To this end, murine NIH3T3 or human HaCaT cells were seeded to confluence, but below their saturation density to allow the establishment of cell-cell contacts without inducing quiescence. Cells were then treated with t-BuOOH (50 or 200 µM, respectively). We revealed that cell-cell contacts reduce basal and t-BuOOH-triggered lipid peroxidation and consequently block ferroptosis. Similar results were obtained with the specific ferroptosis inducer erastin. Cell-cell contacts further protect against t-BuOOH-induced loss of mitochondrial membrane potential, and formation of DNA double-strand breaks. Interestingly, cell-cell contacts failed to prevent t-BuOOH-mediated replication block or formation of the oxidative base lesion 8-oxo-dG. Since evidence of protection against cell death was both (i) observed after treatment with hydrogen peroxide, methyl methanesulfonate or UV-C, and (ii) seen in several cell lines, we conclude that protection by cell-cell contacts is a widespread phenomenon. The impact of cell-cell contacts on toxicity might have important implications in cancer chemotherapy.

Full text links

We have located links that may give you full text access.
Can't access the paper?
Try logging in through your university/institutional subscription. For a smoother one-click institutional access experience, please use our mobile app.

For the best experience, use the Read mobile app

Mobile app image

Get seemless 1-tap access through your institution/university

For the best experience, use the Read mobile app

All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.

By using this service, you agree to our terms of use and privacy policy.

Your Privacy Choices Toggle icon

You can now claim free CME credits for this literature searchClaim now

Get seemless 1-tap access through your institution/university

For the best experience, use the Read mobile app