biostudies-literatureUnknown23(1)Linke CUniversitätsmedizin RostockLieselotte Beutel<h4>Background</h4>Arginine auxotrophy constitutes a shortcoming for ~ 30% of glioblastoma multiforme (GBM). Indeed, arginine-depleting therapy using arginine deiminase from Streptococcus pyogenes (SpyADI) has proven activity against GBM in preclinical studies. The good safety profile of SpyADI renders this agent an ideal combination partner for cytostatic therapy.<h4>Methods</h4>In this study, we combined the antineoplastic antibiotic Mithramycin A (MitA) with SpyADI to boost single-agent activity and analyzed underlying response mechanisms in-depth.<h4>Results</h4>MitA monotherapy induced a time- and dose-dependent cytotoxicity in eight patient-derived GBM cell lines and had a radiosensitizing effect in all but one cell line. Combination treatment boosted the effects of the monotherapy iCancer cell international38https://www.ebi.ac.uk/biostudies/studies/S-EPMC9969664biostudies-literatureThe addition of arginine deiminase potentiates Mithramycin A-induced cell death in patient-derived glioblastoma cells via ATF4 and cytochrome C.PMC9969664Riess CMaletzki CScheffler JVBergmann WFiedler TLinke CSchoenwaelder NDel Moral KFiebig AKaps PFreitag TSchneider BClassen CFDubinski DfalseThe addition of arginine deiminase potentiates Mithramycin A-induced cell death in patient-derived glioblastoma cells via ATF4 and cytochrome C.<h4>Background</h4>Arginine auxotrophy constitutes a shortcoming for ~ 30% of glioblastoma multiforme (GBM). Indeed, arginine-depleting therapy using arginine deiminase from Streptococcus pyogenes (SpyADI) has proven activity against GBM in preclinical studies. The good safety profile of SpyADI renders this agent an ideal combination partner for cytostatic therapy.<h4>Methods</h4>In this study, we combined the antineoplastic antibiotic Mithramycin A (MitA) with SpyADI to boost single-agent activity and analyzed underlying response mechanisms in-depth.<h4>Results</h4>MitA monotherapy induced a time- and dose-dependent cytotoxicity in eight patient-derived GBM cell lines and had a radiosensitizing effect in all but one cell line. Combination treatment boosted the effects of the monotherapy i2023-01-01T00:00:00Z2023 Feb2025-05-29T19:45:04.699Z2025-04-07T00:32:41.678ZS-EPMC99696643684300210.1186/s12935-023-02873-2