Biochemical, apoptotic, necrotic effects of nanoparticles forms with ferrous compounds, silver nitrate and titanium dioxide on cancer cells

Metal compounds and metal nanoparticles has great importance at cancer treatment. Cisplatin is one of the most successful anticancer metal compounds. But researchers have focused on different metal compounds because of side effects. In this thesis, it was aimed to clarify cytotoxic, antiproliferative effects of silver nitrate, titanium dioxide and iron oxide nanopowders and the genes responsible for cell death mechanisms (such as apoptosis, necrosis, autophagy) on A549 cell lines. Cytotoxicity was determined by MTT (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide) assay. Early/late apoptotic-necrotic cell numbers were detected with Annexin V-FITC/PI (Propidium iodid) staining by flow cytometry. Apoptotic effects were determined together with caspase-3 and mitochondrial membrane potential (JC-1) assay. The amount of apoptotic cells were scored by hematoxylin/eosine, TUNEL (Terminal deoxynucleotidyl transferase dUTP nick end labeling), BrdU (Bromodeoxyuridine), Bcl-2 and Bax staining. Cell death pathways were morphologically shown by transmission electron and confocal microscopy. The genes responsible for cell death pathways (apoptosis etc.) were detected by determining amount of activity and increased-reduced expression with microarray assay. AgNO3, TiO2 and Fe3O4 nanopowders are potent cytotoxic and apoptotic agents and may be used as alternative cancer chemotherapeutics.