Cancers, Vol. 15, Pages 5225: Carbonic Anhydrase Inhibitors Induce Ferroptosis through Inhibition of AKT/FTH1 Signaling in Ewing Sarcoma Tumor Cells

Cancers, Vol. 15, Pages 5225: Carbonic Anhydrase Inhibitors Induce Ferroptosis through Inhibition of AKT/FTH1 Signaling in Ewing Sarcoma Tumor Cells Cancers doi: 10.3390/cancers15215225 Authors: Darya Fayzullina Semyn Yakushov Kamilla Kantserova Elizaveta Belyaeva Denis Aniskin Sergey Tsibulnikov Nafisa Fayzullina Stanislav Kalinin Olga Romantsova Peter S. Timashev Brett A. Schroeder Ilya V. Ulasov Ewing sarcoma (ES) is one of the most frequent types of malignant tumors among children. The active metabolic state of ES cells presents a new potential target for therapeutic interventions. As a primary regulator of cellular homeostasis, carbonic anhydrases (CAs; EC 4.2.1.1) have emerged as promising molecular targets for the development of anticancer drugs. Within the present study, we tested the commercial drug acetazolamide and our previously discovered inhibitors to target the CAII isoform, which was overexpressed and positively correlated with ES patient relapse. We employed molecular biology tests to identify effective inhibitors of CAII that can induce ferroptosis by downregulating FTH1 expression in ES cells. In vitro, we have also demonstrated their ability to reduce cell proliferation, decrease invasion, and induce apoptosis- or autophagy-related cell death. Using Western blotting, we confirmed the induction of cathepsin B in cells treated with CA inhibitors. It was found that the suppression of cathepsin B expression during the treatment re...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research