Dehydroascorbic acid sensitizes cancer cells to system x_c^- inhibition-induced ferroptosis by promoting lipid droplet peroxidation.

ABSTRACT: Since the discovery of ferroptosis, it has been postulated that this type of cell death could be utilized in treatments for cancer. Unfortunately, several highly aggressive tumor models are resistant to the pharmacological induction of ferroptosis. However, with the use of combined therapies, it is possible to recover sensitivity to ferroptosis in certain cellular models. Here, we discovered that co-treatment with the metabolically stable ferroptosis inducer imidazole ketone erastin (IKE) and the oxidized form of vitamin C, dehydroascorbic acid (DHAA), is a powerful therapy that induces ferroptosis in tumor cells previously resistant to IKE-induced ferroptosis. We determined that DHAA and IKE + DHAA delocalize and deplete GPX4 in tumor cells, specifically inducing lipid droplet peroxidatio

SUBMITTER: Ferrada L 

PROVIDER: S-EPMC10522586 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature