Synthesis of a Novel Gold(I) Complex and Evaluation of Its Anticancer Properties in Breast Cancer Cells

Abstract

Background: Platinum complexes are commonly used for cancer chemotherapy; however, they are not only highly-priced but also have various side effects. It is, therefore, important to design affordable anticancer drugs with minimal side effects. background: Platinum complexes are commonly used for cancer chemotherapy however they are not only highly priced but also have various side effects. It is therefore important to design affordable anticancer drugs with minimal side effects. Methods: We synthesized a new gold(I) complex, PF6{(BDPEA)(TPPMS) digold(I)} (abbreviated as PBTDG) and tested its cytotoxicity of MCF-7 breast cancer cells. We also evaluated the effects of PBTDG on mitochondrial membrane potential, generation of reactive oxygen species (ROS) and apoptosis in breast cancer cells. objective: To synthesize a novel gold(I) complex and test its cytotoxicity and apoptotic potential in MCF-7 breast cancer cells. Results: The IC50 values for PBTDG and sorafenib were found to be 1.48 μM and 4.45 μM, respectively. Exposure to PBTDG caused significant and concentration-dependent depletion of ATP and disruption of mitochondrial membrane potential. PBTDG induced 2.6, 3.6, and 5.7-fold apoptosis for 1 μM, 3 μM, and 10 μM concentrations, respectively. The induction of apoptosis by the same concentrations of sorafenib was 1.2, 1.3, and 1.6-fold, respectively. The low concentration of PBTDG (1 μM) induced the generation of ROS by 99.83%, which was significantly higher than the ROS generation caused by the same concentration of sorafenib (73.76%). The ROS induction caused by higher concentrations (5 μM) of PBTDG and sorafenib were 104.95% and 122.11%, respectively. method: We synthesized a new gold(I) complex, PF6{(BDPEA)(TPPMS)digold(I)} (abbreviated as PBTDG) and tested the cytotoxicity in MCF-7 breast cancer cells using MTT assay. We used spectrophotometry for ATP analysis and flow cytometry for mitochondrial potential, apoptosis and ROS analyses. Conclusion: The lower concentration of PBTDG produced similar cytotoxicity and apoptotic effects that were caused by a comparatively higher concentration of known anticancer drug (sorafenib). The anticancer effects of PBTDG are attributed to its tendency to disrupt mitochondrial membrane potential, induction of apoptosis and generation of ROS. Further studies are warranted to test the anticancer effects of PBTDG in animal models of cancer. result: The IC50 values for PBTDG and sorafenib were found to be 1.48 μM and 4.45 μM, respectively. Exposure to PBTDG caused significant and concentration-dependent depletion of ATP and disruption of mitochondrial membrane potential. PBTDG induced 2.6, 3.6, and 5.7-folds apoptosis for 1 µM, 3 µM, and 10 µM concentrations, respectively. The induction of apoptosis by same concentrations of sorafenib was 1.2, 1.3, and 1.6-folds, respectively. The low concentration of PBTDG (1 µM) induced the generation of reactive oxygen species (ROS) by 99.83% which was significantly higher than the ROS generation caused by the same concentration of sorafenib (73.76%). The ROS induction caused by higher concentration (5 µM) of PBTDG and sorafenib were 104.95% and 122.11%, respectively. other: Further studies are warranted to test the anticancer effects of PBTDG in animal models of cancer.