Anti-proliferative effects of a copper(II) complex with a thiosemicarbazone ligand against selected human cancer cells

Date

2023

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Sankpal, Umesh
Alajroush, Duaa
Smith, Chloe
Anderson, Brittney
Mann, Novia
Beebe, Stephen
Holder, Alvin
Basha, Riyaz

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Purpose: The frequent relapse and drug resistance associated with the current cancer chemotherapy treatments necessitate the development of alternative strategies. Thiosemicarbazones are a class of metal chelators that have been explored to treat diverse human diseases, including cancer. Copper, a crucial structural component for many significant enzymes and a key catalytic co-factor in redox processes, is being explored for several medical applications. Additionally, the anti-cancer activity of certain chemotherapeutic agents can be enhanced by the use of copper-containing complexes. This study aimed to evaluate the antiproliferative effects of a copper(II) complex with a thiosemicarbazone ligand (Cu-acetylethTSC or [Cu(acetylethTSC)Cl]Cl·0.25C2H5OH (where acetylethTSC = (E)-N-ethyl-2-[1-(thiazol-2-yl)ethylidene]hydrazinecarbothioamide)) against human cancer cell lines, viz., medulloblastoma (DAOY, D283), glioblastoma (LN-229), Ewing sarcoma (TC205, CHLA10), and acute lymphoblastic leukemia (CCRF-CEM, SUP-B15). Methods: These selected cell lines were cultured using standard protocols. Cell viability was measured using a Cell Titer-Glo kit at 48 h after treatment with various concentrations of Cu-acetylethTSC. Each treatment group and the controls were read in triplicates and the data were plotted as percentage cell viability versus concentration of the complex. Dose-response curves were generated based on the cell viability data obtained, and IC50 values were calculated. Cardiomyocytes (H9C2) were also cultured and used to test cytotoxicity in non-malignant cells. Results: Cell viability was inhibited in a dose-dependent manner in all the selected cancer cell lines whiles that of H9C2 was not significantly affected. Conclusion: This indicates that Cu-acetylethTSC was selective for malignant cells. Further studies are underway to understand the efficacy, protein targets, and underlying mechanisms of the role of Cu- acetylethTSC.

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