Abstract
Abstract Urokinase-type plasminogen activator (uPA) system may play a crucial role in cancer cell invasion and metastasis. uPA has been validated as a predictive or prognostic biomarker protein and considered as a therapeutic target in human breast cancer. Mesupron is a uPA inhibitor blocking uPA enzymatic activity to reduce tumor cell invasion, migration and cell growth. Auranofin has been known as an antirheumatic drug and a thioredoxin reductase inhibitor and recently its anticancer activity in ovarian and breast cancers has also been identified. To study whether cotreatment with mesupron and auranofin shows a significant anticancer activity, the synergistic induction of apoptosis of mesupron with auranofin was determined. Auranofin or mesupron alone inhibited cancer cell growth in MCF-7 cells with IC50 of 0.25 μM or 25 μM, respectively. Flow cytometric analysis also showed an increased apoptosis. When cells were treated with mesupron (0.125 μM) in combination with auranofin (10 μM), we found a significant induction of apoptosis although the cytotoxic effects of mesupron or auranofin alone at those concentrations were not quite strong. Interestingly, combined mesupron and auranofin treatment significantly suppressed mitochondrial antiapoptotic proteins including Bcl-2 and Bcl-xL. We also found the increase of caspase-3 and PARP cleavages. The combination index (CI) also indicated the synergistic induction of apoptosis by auranofin and mesupron. Taken together, these data suggest that the use of mesupron and auranofin in combination can be valuable to achieve higher anticancer activity. Note: This abstract was not presented at the meeting. Citation Format: Joo-Eun Lee, Yeo-Jung Kwon, Kyung-Soo Oh, Young-Jin Chun. Synergistic induction of apoptosis of combined mesupron and auranofin treatment in human breast cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2020. doi:10.1158/1538-7445.AM2017-2020
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