Furanokumarin Bileşiklerinden Olan Bergaptol'ün Antikanser Potansiyelinin Araştırılması

Abstract

Furanocoumarins are natural compounds produced by many plants and have been used therapeutically for centuries in eastern countries. Today, furanocoumarins are widely studied as antiseptics, neuroprotectives, osteoprotectives and antioxidants. Cancer is recognized as one of the most serious medical conditions in the world, causing millions of deaths each year in both developed and developing countries. Although chemotherapy and radiotherapy, which are the most preferred methods among the current treatment approaches, are effective treatment approaches, they bring many physical and psychological difficulties for the patient. At the same time, the resistance mechanisms developed by cancer cells against chemotherapeutics may also lead to unsuccessful treatments. For the above-mentioned reasons, it is essential to develop new and effective treatment approaches against the increasing number of cancer cases. Agents developed using natural products are good alternatives in this regard. In this thesis, the anticancer potential of bergaptol, a furanocoumarin compound, was evaluated in three different cancer cell lines, MDA-MB-231, HepG2, HeLa cell lines and its anti-angiogenic potential was evaluated using HUVEC cells in three-dimensional culture (3D). In this context, in order to investigate the anticancer effects of bergaptol, experimental studies were carried out under two-dimensional (2D) cell culture conditions in which viability was examined by MTT and AO/PI assays, apoptosis by Annexin V/PI assays, and cell cycle by BrdU and Cytophase Violet assays. Then, in order to evaluate the anti-angiogenic activity of bergaptol in 3D culture conditions, HUVEC cells were labeled with CFSE to form multicellular microtissues and flow cytometry and confocal microscopy analyses were performed following bergaptol treatment. The data obtained showed that bergaptol caused high cytotoxicity in cancer cells and endothelial cells, whereas it had no toxic effect on healthy cells. When the mechanism underlying this toxic effect was examined, it was found that there was an increase in the rate of apoptotic cells after bergaptol administration, and in addition to this increase, cell proliferation was suppressed with cell cycle inhibition. As a result of 3D cell culture studies; after bergaptol application to micro tissues, cell viability decreased, and spheroid diameters decreased. At the same time, HUVEC cells labeled in 3D microtissues were critically reduced after bergaptol treatment. Taken together, it was concluded that bergaptol has high anti-cancer and anti-angiogenic potential.