Presentation of STSM: Investigation of inhibitory properties of Michael acceptors on thioredoxin reductase 1 inhibition in vitro

Abstract

Cancer cells have increased level of reactive oxygen species (ROS), due to metabolic changes following their growth and development; they have adapted to increase in ROS by different mechanism, in part by increasing activity of antioxidant systems. Main antioxidant systems in a living cell are thioredoxin and glutharedoxin systems. Thioredoxin system is mainly comprised of thioredoxin and thioredoxin reductase. It has been reported that cytosolic thioredoxin reductase, TrxR1, has increased activity in cancer cells. Inhibition of TrxR1 could have a detrimental effect on cancer cell survival, due to further increase of ROS. Development of new TrxR1 inhibitors gives possibilities in new therapeutic approaches in treating cancer, as an accompanying treatment to conventional treatment strategies. STSM was realized in collaboration between home institution, Institute for Biological Research "Siniša Stanković" - National Institute of Republic of Serbia, University of Belgrade and host institution, Latvian Institute of Organic Synthesis (Riga, Latvia). Purpose of the STSM was to evaluate inhibitory properties of 6 potential inhibitors of thioredoxin reductase 1 on neuroblastoma cell line SHSY5Y. This particular cell line was chosen as it proved to be a good model for studying Trx system. Potential inhibitors were tested for inhibitory properties of TrxR on crude protein cell lysate of SHY5Y, rat TrxR1 enzyme and on insulin assay. Main result of this STSM is selection of the best candidate for further expansion series in studying Michael acceptors as inhibitors of TrxR1 and possible applications in anti-cancer therapy. The results obtained during STSM were published in a peer-reviewed journal [1]. This STSM is a perspective start to further investigation of importance of thioredoxin reductase 1 in cancer cell survival and inhibition of TrxR1 in cancer therapy. The candidate-inhibitors will in future be tested on cancer cell lines and multidrug resistant cancer cell models, with different antioxidant capacities.