| Autor: |
Wen M; Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, China., Deng ZK; Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, China., Jiang SL; Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, China., Guan YD; Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, China., Wu HZ; Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, China., Wang XL; Translational Medicine R&D Center, Institute of Biomedical and Health Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China., Xiao SS; Department of Gynecology and Obstetrics, The Third Xiangya Hospital, Central South University, Changsha, China., Zhang Y; Department of Pharmacology, College of Pharmaceutical Sciences, Soochow University, Suzhou, China., Yang JM; Department of Pharmacology, The Penn State Hershey Cancer Institute, The Pennsylvania State University College of Medicine and Milton S Hershey Medical Center, Hershey, PA, United States., Cao DS; Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, China.; Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China., Cheng Y; Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, China.; Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China. |
| Abstrakt: |
Bcl-2 family protein is an important factor in regulating apoptosis and is associated with cancer. The anti-apoptotic proteins of Bcl-2 family, such as Bcl-2, are overexpression in numerous tumors, and contribute to cancer formation, development, and therapy resistance. Therefore, Bcl-2 is a promising target for drug development, and several Bcl-2 inhibitors are currently undergoing clinical trials. In this study, we carried out a QSAR-based virtual screening approach to develop potential Bcl-2 inhibitors from the SPECS database. Surface plasmon resonance (SPR) binding assay was performed to examine the interaction between Bcl-2 protein and the screened inhibitors. After that, we measured the anti-tumor activities of the 8 candidate compounds, and found that compound M1 has significant cytotoxic effect on breast cancer cells. We further proved that compound M1 downregulated Bcl-2 expression and activated apoptosis by inducing mitochondrial dysfunction. In conclusion, we identified a novel Bcl-2 inhibitor by QSAR screening, which exerted significant cytotoxic activity in breast cancer cells through inducing mitochondria-mediated apoptosis. |
