Investigation of cytotoxic and apoptotic effects of Zn(II) complex in cancer cells

Cancer is a disease caused by uncontrolled proliferation of cells. This process begins with the mutation of cells due to various risk factors and unlimited proliferation. Recent studies have shown that metal-based compounds are promising in the treatment of cancer. Especially metal complexes such as platinum (Pt), silver (Ag), gold (Au) and zinc (Zn) have been used in many anticancer studies and successful results have been obtained. Therefore, the anticancer effects of a Zn(II) complex in human breast cancer cells and the mechanisms responsible for these effects were investigated in this thesis. The anti-proliferative potential of Zn(II) complex in human breast cancer cells was determined by SRB viability test. Cell viability was confirmed by ATP viability test. The possible cytotoxic effect of the complex was also evaluated in healthy human breast cells. Hoechst 33342 / Propidium Iodide dual staining method and broken cytokeratin-18 (M30 antigen level) method were used to demonstrate the presence of cell death mechanism and apoptosis responsible for cytotoxic effects. Expression levels of cell death-related proteins (B-Actin, PARP/cleaved PARP, COX4, DR4, Prokaspas-8 / cleaved Kaspas-8, BAX, RIP) were demonstrated by immunoblotting. Apoptosis-related gene expression was determined using Polymerase Chain Reaction. Wound healing test was performed to determine the effect of Zn(II) complex on cell migration. In addition, the cytotoxic effect of Zn(II) complex on cancer stem cells was investigated on mamospheres rich in stem cell population. The results showed that Zn(II) complex caused cytotoxic effect in human breast cancer cells depending on dose and time and was not toxic in healthy cells. Zn(II) complex induces apoptosis in cancer cells was determined at both protein and gene levels. Zn(II) complex significantly inhibited the migration ability of cancer cells. Zn(II) complex also had cytotoxic activity in cancer stem cells. When all the results were evaluated, it was concluded that further analysis should be performed with the assumption that Zn(II) complex can be used as a promising agent in the treatment of cancer.