Investigation of the Apoptosis Inducing and β-catenin Silencing by Tetradentate Schiff Base Zinc(II) Complex on the T-47D Breast Cancer Cells.

Abstract

Several mechanisms are known for the anticancer effects of cisplatin. However, its most wellknown function involves binding to DNA and activating the DNA damage response. Despite its good effects, the treatment process often leads to chemoresistance and affects the mechanisms that support cell survival, such as pathways that promote cell growth, apoptosis, DNA damage repair, and endocytosis. For this reason, we investigated the effects of a new metal complex (tetradentate Schiff base zinc(II) complex) on breast cancer cells (T-47D). We evaluated its effect on cytotoxicity, apoptosis, and drug resistance in comparison to cisplatin. The results of the MTT test showed that tetradentate Schiff base zinc(II) complex has good cytotoxicity compared to cisplatin. The IC50 values for the [Zn(SB)]Cl2 complex and cisplatin after 72 h of exposure were equal to 42.1 and 276.1 μM, respectively. Real-time PCR assay confirmed that the [Zn(SB)]Cl2 complex activated the mitochondrial pathway of apoptosis and increased the expression of Bak1 and caspase-3 genes significantly compared to cisplatin. More importantly, the [Zn(SB)]Cl2 was able to reduce the expression of the β-catenin gene, which plays a role in drug resistance, by 0.011 compared to the control. Therefore, we can hope for this new complex because, without the help of any β-catenin silencing agent, it was able to inhibit the drug resistance in the T-47D cell line that overexpresses the β-catenin gene.