Study on the Cytotoxic Effects, Apoptosis Induction, Treatment Resistance, and Inflammation Caused by a Gold(III) Complex Containing 3,4-diaminobenzophenone and 2,3-butanedione Monoxime on the Esophageal Cancer Cell Line KYSE-30.

内容摘要

Given the known therapeutic properties of gold compounds such as auranofin, this study aimed to evaluate the anticancer potential of a newly synthesized gold(III) Schiff base complex. We hypothesized that this complex could selectively induce apoptosis in cancer cells while minimizing inflammatory responses in normal cells. A gold(III) complex bearing a tetradentate Schiff base ligand was synthesized, and its cytotoxicity was assessed using MTT assay and sulforhodamine B staining. KYSE-30 esophageal cancer cells and NIH/3T3 normal fibroblasts were treated with the complex and compared to cisplatin. Gene expression analysis was performed to evaluate apoptotic and inflammatory genes. The gold(III) Schiff base complex significantly inhibited KYSE-30 cell proliferation more effectively than cisplatin after 48 hours. Unlike cisplatin, it did not induce cytotoxicity in NIH/3T3 cells. The complex elevated the BAK1/Bcl-xL ratio by 2.22-fold, suggesting activation of the intrinsic mitochondrial apoptotic pathway, which was not observed with cisplatin. It also downregulated the anti-apoptotic Bcl-xL gene (0.662-fold) and the resistance-associated AKT1 gene (0.0544-fold). Both the gold(III) Schiff base complex and cisplatin activated the extrinsic apoptotic pathway via Caspase-3. Importantly, neither compound induced TNF-α expression, indicating no inflammatory response in normal cells. These findings demonstrate that the gold(III) Schiff base complex selectively targets esophageal cancer cells through dual apoptotic pathways while sparing normal cells from cytotoxicity and inflammation. Its ability to suppress resistance-related genes further highlights its therapeutic promise. The gold(III) Schiff base complex represents a compelling alternative to cisplatin, offering enhanced anticancer efficacy, reduced toxicity to normal cells, and minimal inflammatory activation. Further investigation into its clinical potential is warranted.