The Cytotoxic Effect of a Cu(II) Complex with Thiosemicarbazone Ligand on Triple Negative Breast Cancer

College

College of Sciences

Department

Chemistry and Biochemistry

Graduate Level

Doctoral

Presentation Type

Oral Presentation

Abstract

Abstract

Breast cancer, characterized by the uncontrolled growth of abnormal cells in the breast, poses a significant health challenge. Triple negative breast cancer (TNBC) is a subtype of breast cancer and characterized by the absence of three receptors commonly found in breast cancer cells: estrogen, progesterone, and HER2 receptors. Therapeutic options for treating TNBC are limited, and the chemotherapeutic drug, cisplatin, reported various side effects. Copper-containing complexes with thiosemicarbazones (TSCs) ligands have shown great potential in anti-cancer properties when compared to cisplatin. The current research involved a study of the cytotoxic effects of copper(II) complex [Cu(chromoneTSC)Cl2]•0.5H2O•0.0625C2H5OH (where chromoneTSC = (E)-N-Ethyl-2-((4-oxo-4H-chromen-3-yl)methylene)-hydrazinecarbothioamideand) and its “free” ligand, chromoneTSC, as well as cisplatin as a positive control on a human breast cancer MDA-MB-231 VIM RFP cell line. The cytotoxicity study was carried out by using a WST-8 based Cell Counting Kit-8 (CCK-8) assay. The IC50 values with the use of the “free” ligand, chromoneTSC, were 40.7 ± 3.2, 35.8 ± 1.6, and 31.5 ± 1.4 mM, at 24, 48, and 72 h, respectively. With cisplatin, the IC50 values were 30.6 ± 3.5, 23.7 ± 2.6, and 21.6 ± 1.9 mM at 24, 48, and 72 h, respectively. Intriguingly, the Cu(II) complex demonstrated a significant cytotoxic effect, as evidenced by the low IC50 values of 21.3 ± 2.7, 19.2 ± 2.8, and 15.8 ± 3.1 mM at 24, 48, and 72 h of treatment, respectively. These findings indicated the potential anti-cancer activity of the Cu(II) complex when compared to the “free” ligand and cisplatin. Future studies will investigate the cytotoxic effect of these compounds on non-cancerous MCF-10A cells and to study the cell death mechanisms induced after treatment, viz., apoptosis, pyroptosis, and necroptosis. This holistic approach aims to deepen our understanding of the compounds' therapeutic potential and to pave the way for more targeted and efficacious breast cancer treatments.

Keywords

Triple negative breast cancer, cisplatin, chromoneTSC, and Cu(II) complex.

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The Cytotoxic Effect of a Cu(II) Complex with Thiosemicarbazone Ligand on Triple Negative Breast Cancer

Abstract

Breast cancer, characterized by the uncontrolled growth of abnormal cells in the breast, poses a significant health challenge. Triple negative breast cancer (TNBC) is a subtype of breast cancer and characterized by the absence of three receptors commonly found in breast cancer cells: estrogen, progesterone, and HER2 receptors. Therapeutic options for treating TNBC are limited, and the chemotherapeutic drug, cisplatin, reported various side effects. Copper-containing complexes with thiosemicarbazones (TSCs) ligands have shown great potential in anti-cancer properties when compared to cisplatin. The current research involved a study of the cytotoxic effects of copper(II) complex [Cu(chromoneTSC)Cl2]•0.5H2O•0.0625C2H5OH (where chromoneTSC = (E)-N-Ethyl-2-((4-oxo-4H-chromen-3-yl)methylene)-hydrazinecarbothioamideand) and its “free” ligand, chromoneTSC, as well as cisplatin as a positive control on a human breast cancer MDA-MB-231 VIM RFP cell line. The cytotoxicity study was carried out by using a WST-8 based Cell Counting Kit-8 (CCK-8) assay. The IC50 values with the use of the “free” ligand, chromoneTSC, were 40.7 ± 3.2, 35.8 ± 1.6, and 31.5 ± 1.4 mM, at 24, 48, and 72 h, respectively. With cisplatin, the IC50 values were 30.6 ± 3.5, 23.7 ± 2.6, and 21.6 ± 1.9 mM at 24, 48, and 72 h, respectively. Intriguingly, the Cu(II) complex demonstrated a significant cytotoxic effect, as evidenced by the low IC50 values of 21.3 ± 2.7, 19.2 ± 2.8, and 15.8 ± 3.1 mM at 24, 48, and 72 h of treatment, respectively. These findings indicated the potential anti-cancer activity of the Cu(II) complex when compared to the “free” ligand and cisplatin. Future studies will investigate the cytotoxic effect of these compounds on non-cancerous MCF-10A cells and to study the cell death mechanisms induced after treatment, viz., apoptosis, pyroptosis, and necroptosis. This holistic approach aims to deepen our understanding of the compounds' therapeutic potential and to pave the way for more targeted and efficacious breast cancer treatments.