Abstract 2287 The arsenic-containing compound 2-amino-4-arsinobutyric acid exhibits anti-cancer effects by inhibiting glutaminase

Breast cancer is the leading cause of cancer death in women, according to the National Cancer Institute (NCI). Triple negative breast cancer (TNBC) cells do not respond to treatments such as hormones, monoclonals, and tyrosine kinase inhibitors due to lack of progesterone and estrogen receptors. However, despite intensive drug discovery efforts, there is still no approved targeted treatment for TNBC. The results of our study indicate that a trivalent arsenic-containing amino acid, R-AST-OH (2-amino-4-arsinobutyric acid), inhibits kidney-type glutaminase (KGA), the enzyme responsible for glutamine metabolism that is associated with tumor malignancy. The results of TNBC cell-based assays using MDA-MB-231 and HCC1569 cells showed that R-AST-OH kills TNBC cells but is not cytotoxic to non-cancerous control cell lines. Based on the in silico docking analysis, we predict that R-AST-OH forms irreversible As-S bonds with cysteine residues in KGA Overall, R-AST-OH is a promising lead compound for the development of new treatment options for TNBC. This work was supported by a pilot project grants from the Research Center in Minority Institutions, Florida International University (1U54MD012393-03) and Florida Breast Cancer Foundation (AWD 15620) to V.S.N. and NIH grant R35GM136211 to B.P.R.