Selenium modulates cancer cell response to pharmacologic ascorbate

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Selenium modulates cancer cell response to pharmacologic ascorbate

Post Number:#1  Post by ofonorow » Wed Aug 03, 2022 9:52 am

https://aacrjournals.org/cancerres/article-abstract/doi/10.1158/0008-5472.CAN-22-0408/707364/Selenium-modulates-cancer-cell-response-to?redirectedFrom=fulltext

Selenium protects cancer cells, so vitamin C against cancer is enhanced when selenium deficient.

Abstract

High-dose ascorbate (vitamin C) has shown promising anti-cancer activity. Two redox mechanisms have been proposed: hydrogen peroxide generation by ascorbate itself or glutathione depletion by dehydroascorbate (formed by ascorbate oxidation). Here we show that the metabolic effects and cytotoxicity of high-dose ascorbate in vitro result from hydrogen peroxide independently of dehydroascorbate. These effects were suppressed by selenium through antioxidant selenoenzymes including glutathione peroxidase 1 (GPX1) but not the classic ferroptosis-inhibiting selenoenzyme GPX4. Selenium-mediated protection from ascorbate was powered by NADPH from the pentose phosphate pathway. In vivo, dietary selenium deficiency resulted in significant enhancement of ascorbate activity against glioblastoma xenografts. These data establish selenoproteins as key mediators of cancer redox homeostasis. Cancer sensitivity to free radical-inducing therapies, including ascorbate, may depend on selenium, providing a dietary approach for improving their anticancer efficacy.
Owen R. Fonorow
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