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 168nm and 27.5mV, respectively. The NPs had spherical shape and were in a size range of 10 to 60nm in diameter. This work revealed that CuO@Glu/TSC NPs efficiently inhibited the proliferation of AGS cells with significantly lower IC50 value (203µg/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 studies.
Highlights
Gastric cancer is a prevalent and deadly cancer, with about one million annual new cases, in the world [1]
A similar protocole was used for the synthesis of Cuo@Glu, but 150 mg of Lglutamic acid was added to the reaction mixture
The band at 1607 cm–1 corresponds to the C=O vibration of −COOH groups for glutamic acid on the surface of CuO NPs
Summary
Gastric cancer is a prevalent and deadly cancer, with about one million annual new cases, in the world [1]. Gastric cancer causes 783.000 deaths annually, which accounts for 8.3 % of cancer-associated death [1]. Finding novel and inexpensive anticancer agents with minimal side effects is crucially important to treat gastric cancer. As a novel and efficient anticancer agent, many efforts have been focused on finding metal-containing drugs [3]. Copper complexes have gained more attention due to their fewer side effects and toxicity. Due to the increased copper uptake by cancer cells, the preparation of antiproliferative copper complexes might provide selective toxicity against cancer cells
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