Investigation of the anti-cancer activities of some agents with potential use in photodynamic therapy

Cancer has been one of the deadliest diseases in the world for many years. Although there are many types of cancer, according to the statistical data published by the World Health Organization, breast cancer, ovarian cancer and colorectal cancer are cancer types that constitute a significant burden all over the world. Traditional treatment types such as radiotherapy, surgery and chemotherapy are applied for the treatment of cancer patients. However, these treatment modalities can not completely prevent the metastasis and recurrence of cancer in some cases. Therefore, research studies continue for more effective cancer treatment methods. Photosensitizers used in photodynamic therapy, which is based on the integration of light with chemicals and known as a new cancer treatment method, can reach cancer cells in the body by applying topically or intravenously, and minimize the negative effects on healthy body cells since they tend to accumulate in cancer cells and are a local treatment method. Within the scope of the thesis, it is aimed to examine the anticancer properties of Aza-BODIPY-based new generation photosensitizer molecules, which have the potential to be used in photodynamic therapy, on MCF-7, OV2008 and HT29 cell lines. Iodine was bonded by halogenation by taking advantage of the designable feature of the aza-BODIPY molecule, which is one of the photosensitizers used in photodynamic therapy. By iodine binding, it is aimed to increase the singlet oxygen yield with the increase of the fluorescence efficiency and cutaneous efficiency of the aza-BODIPY molecule. Compounds such as chitocene are known to be used in controlled drug delivery systems. Thanks to this feature of chitose, the usability of the compounds to be used in the thesis at low doses has been investigated. For this purpose, cell viability and metabolic activity of the compounds were determined by MTT assay, while cell damage and cell membrane integrity were determined by LDH assay. In addition, the mechanism of cell death triggered by the cytotoxic effects of the compounds used on the cells was partially revealed by flow cytometry analysis. It was observed that Aza-BODIPY-based new generation photosensitizer molecules exhibited both similar and different effects in three different cancer cell lines, depending on the concentration and whether they contained chitocene. Of the compounds used, only L2 ligands showed a high cytotoxic effect when PDT was applied to all three cell lines. The L1 series for OV2008 and the L2 series for HT29 produced significant results for FDT in chitocene added compounds. Among the three cell lines, it was found to be more sensitive to FDs using HT29. It was determined that L2 ligands without chitocene and L2 ligand with chitosen and L2 complexes decreased LDH secretion in the study with HT29 cell line, while L2-NIS ligand with chitocene caused damage to the cell membrane and increased LDH secretion. Flow cytometry analysis revealed that L2 ligand and compounds with NIS triggered more apoptosis in the HT29 cell line. In addition, when cell morphologies were examined, cell membrane damage and apoptotic bodies were observed in OV2008 and HT29 cell lines, while the study with MCF-7 cell line mostly preserved cell membrane integrity.