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, ow 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 con rmed by the XRD pattern. The EDX analysis con rmed 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 e ciently inhibited the proliferation of AGS cells with signi cantly 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 signi cantly increased by 1.4 folds. This study introduced CuO@Glu/TSC as an e cient anticancer against gastric cancer cells with lower toxicity toward normal cells which could be employed for cancer treatment after further characterization.

Addressing the gaps in homeostatic mechanisms of copper and copper dithiocarbamate complexes in cancer therapy: a shift from classical platinum-drug mechanisms

“…[72][73][74] Several copper bis(thiosemicarbazone) conjugates have shown promising anticancer properties. [75][76][77][78] Cu 2+ (atsm) is one of these complexes that retains its bonded metal in a reductive intracellular environment. Palanimuthu and coworkers (2013) chose two variants, copper(gtsc) (7) and copper(gtsc•HCl) (8), for their powerful anticancer effects, which was comparable to that of the widely used chemotherapeutic agent adriamycin.…”

Hippophae rhamnoides L. (sea buckthorn) mediated green synthesis of copper nanoparticles and their application in anticancer activity

“…A team led by Badrooh developed a spherical-shaped complex of TSC and CuNPs whose size was varying from 10 to 60 nm that can trigger the apoptosis of Adenocarcinoma gastric. The study proved that the synthesized complex proficiently depleted the augmentation of AGS cells with significantly reduced IC 50 reading (203 μg/mL) than HEK293 (IC 50 = 435 μg/mL) ( Badrooh et al, 2022 ).…”

Downregulated Copper Homeostasis-Related Gene FOXO1 as a Novel Indicator for the Prognosis and Immune Response of Breast Cancer

“…In addition, researchers observed that Cu levels were higher in the serum and tissues than those in healthy control groups when cancer patients were in advanced stages [ 24 ]. Likewise, previous studies implied a higher demand for Cu in cancer cells, which would be a breakthrough point to slow cancer progression [ 25 ]. Cu is considered a promising anticancer targeting agent [ 26 ].…”