Flurbiprofenin Sitotoksik, Genotoksik ve Apoptotik Etkilerinin Değerlendirilmesi

Abstract

B Bakir, E., Evaluation of Cytotoxic, Genotoxic and Apoptotic Effect of Flurbiprofen, Hacettepe Un¬vers¬ity Graduate School Health Sciences Pharmacy Department of Pharmaceutical Toxicology Doctor of Phi¬losophy Thes¬is, Ankara, 2018. Flurbiprofen is a propionic acid-derived non steroid anti-inflammatory drug. Although there are many studies of the anticancer effects of NSAI drugs, there are few studies of flurbiprofen and the anticancer activity of flurbiprofen is not fully understood. In this study, cytotoxic, genotoxic and apoptotic effects of flurbiprofen were evaluated in human cervical cancer (HeLa) and human liver cancer (HepG2) cell lines. Cytotoxicity was measured at a wide dose range and exposure times with 24, 48 and 72 hours were evaluated. As a result, it was observed that cytotoxicity increased both dose and time dependent in both cell lines. Genotoxicity study was performed with 48 hours exposure time and determined doses. DNA tail length, tail density and tail moment evaluations revealed a dose-dependent increase in DNA damage in cells. Early apoptosis was evaluated at the gene level using real-time polymerase chain reaction (RT-PCR). After 48 hours exposure; increased levels of apoptotic genes p53, Bax, caspase-3 and caspase-9, and decreased levels of BcL-2 and survivin genes, which are antiapoptotic genes. Late apoptosis and cell cycle analyzes were evaluated using flow cytometry. No evidence of late apoptosis was observed in both cells and no significant arrest was observed in the cell cycle. It has been determined that the cells generally exhibit proliferating cell characteristics. As a result, it was observed that flurbiprofen had an apoptotic effect at both the determined doses and at the end of the determined exposure period, but the apoptosis process was not completed yet. Findings from the study indicate that flurbiprofen is effective at gene level and induces apoptosis with intracellular pathway.