Sulfabenzamide promotes autophagic cell death in T-47D breast cancer cells through p53/ DRAM pathway [Sülfobenzamid,T-47D meme kanseri hücrelerinde p53/DRAM yolaǧi{dotless} araci{dotless}li{dotless}ǧi{dotless}yla otofajik hücre ölümünü teşvik eder]

Sulfonamides exhibit their antitumor effects through multiple mechanisms including inhibition of membrane bound carbonic anhydrases,prevention of microtubule assembly,cell cycle arrest,and inhibition of angiogenesis. here,sulfabenzamide's mechanisms of action on t-47d breast cancer cells were determined. cells incubated with sulfabenzamide exhibited negligible levels of apoptosis,necrosis and cell cycle arrest when compared to untreated cells. these results were confirmed by morphological examinations,dna fragmentation assays,flow cytometric and real time rt-pcr analysis. surprisingly,despite negligible detection of dna fragmentation,a considerable increase in caspase-3 activity was observed in cells incubated with sulfabenzamide. the increased expression ratio of dff-45/dff-40 indicated that caspase-3-related dna fragmentation was blocked and apoptosis symptoms could not be seen. however,the effects of caspase-3 for parp1 and dna-pk deactivation resulted in autophagy induction. the overexpression of critical genes involved in autophagy,including atg5,p53 and dram,indicated that in t-47d cells sulfabenzamide-induced antiproliferative effect was mainly exerted through induction of autophagy. furthermore,downregulation of akt1 and akt2 as well as over expression of pten resulted in attenuation of akt/mtor survival pathway showing that death autophagy should be occurred in sulfabenzamide treatment.