Trigger of Apoptosis in Adenocarcinoma Gastric Cell Line (AGS) by a Complex of Thiosemicarbazone and Copper Nanoparticles

Abstract Seeking novel anticancer agents with minimal side effects against gastric cancer is vitally important. Copper, as an important trace element, takes roles in different physiologic pathways. Also, there is a higher demand for copper in cancer cells than normal ones. Copper complexes containing a therapeutic ligand could be promising candidates for gastric cancer chemotherapy. In this work, copper oxide nanoparticles were synthesized, functionalized with glutamic acid (CuO@Glu) and conjugated with thiosemicarbazone (Cuo@Glu/TSC NPs). The NPs were characterized and their antiproliferative potential against AGS cancer cells was investigated using MTT, flow cytometry, Hoechst staining, and caspase 3 activation assays. The FT-IR results showed the proper binding of TSC to CuO@Glu NPs and crystallinity of the prepared NPs was confirmed by the XRD pattern. The EDX analysis confirmed the presence of Cu, N, C, O, and S elements and lack of impurities. The Hydrodynamic size and zeta potential of the Cuo@Glu/TSC NPs were 710 nm and 27.5 mv, respectively. The NPs had spherical shape and were in a size range of 20-39 nm in diameter. This work revealed that CuO@Glu/TSC NPs efficiently inhibited the proliferation of AGS cells with significantly lower IC50 value (203 µg/mL) than normal HEK293 cells (IC50=435µg/mL). Flow cytometry and Hoechst staining obviously revealed apoptosis induction among CuO@Glu/TSC treated cells, and caspase-3 activity significantly increased by 1.4 folds. This study introduced CuO@Glu/TSC as an efficient anticancer against gastric cancer cells with lower toxicity toward normal cells which could be employed for cancer treatment after further characterization.