Abstract 5710: Anticancer effects of 2,3-<i>bis</i>(bromomethyl)-quinoxaline 1,4-dioxide on uterine cancer

Abstract Uterine cancer will claim an estimated 17, 610 lives in the United States in the year 2024. Lack of funding and focus have resulted in little advancement in treatment options for uterine cancer patients. Consequently, uterine cancer incidence and mortality have consistently increased since the 1990’s in the United States. Thus, further investigation and development of uterine cancer therapies is needed. The Peroxiredoxins (I-VI) family of enzymes is responsible for eliminating reactive oxygen species throughout the cell and has been studied in multiple organisms and diseases, including cancer. The compound 2, 3-bis(bromomethyl)-quinoxaline 1, 4-dioxide (Conoidin A) is a Peroxiredoxin II inhibitor that has been studied in the parasite, Toxoplasma gondii. It inhibits the enzymatic activity of Peroxiredoxin II when studied in vitro by covalently binding to cysteine. Recent reports identify Peroxiredoxin II as a potential therapeutic target for cancer therapies and indicate that Peroxiredoxin II down-regulation promotes cancer cell death. Thus, the purpose of these studies was to evaluate Conoidin A as a potential therapeutic for uterine cancer. Here, we report that concentrations of 100 μM, 75 μM, and 50 μM of Conoidin A decreased growth of the uterine cancer cell line, HEC-1-A, after 24 hours as measured using crystal violet assays. Conoidin A concentrations of 100 μM, 75 μM, and 50 μM compromised anchorage-independent growth of HEC-1-A cells in soft agar assays. Furthermore, p53 up-regulation (p53+) correlates with poor prognosis in uterine cancer patients. To determine if Conoidin A is capable of decreasing growth of p53+ tumors, increasing Conoidin A concentrations were tested on the p53+ cell line, C-33a, using crystal violet assays. Preliminary studies found Conoidin A abolishes C-33a growth at concentrations of 100 μM, 75 μM, and 50 μM after 24 hours of treatment. These data identify Conoidin A as a potential therapeutic for uterine cancer, including p53+ tumors. Furthermore, these studies establish Peroxiredoxin II as a novel therapeutic target for this disease. Citation Format: Kaitlyn Mayo, Kennedy Szabo, Calli A. Davison-Versagli. Anticancer effects of 2, 3-bis(bromomethyl)-quinoxaline 1, 4-dioxide on uterine cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 5710.