The effects of caspases on apoptosis in ras-activated cells

THE EFFECTS OF CASPASES ON APOPTOSIS IN RAS-ACTIVATEDCELLSABSTRACTIn this thesis, the changes of morphological and biochemical features and theeffects of kaspaz-3 and kaspaz-9 enzymes on apoptotik mechanism of treatedhuman-U2OS (osteosarcoma) cells were investigated. Beside, the role of integrinreceptors activated by varies of extracellular proteins (fibronectin, collagen,trombospondin-1) on U2OS apoptotic mechanism was also studied in variesaspects.IC50 value of Cis-platin was found 4 µM by cytotoxic studies based onmitocondrial activities. The morphological and nuclear staining studies by usingnon-toxic concentrations range were indicated that the cell membrane ruptures,membrane blebbing, nuclear apoptotic changes and DNA fragmentation werestarted. Kaspaz-9 was found more effective on the apoptotic mechanism of Cis-platin stimulated U2OS cells than kaspaz-3. The variation was observed on theratio of apoptotic U2OS cells with dependent on type of integrin activated.Especially, the apoptotic ratio of fibronectin attached cells was lower than otherproteins used.The investigation of apoptotic mechanism of cis-platin induced U2OS cells andhow the integrins effected during metastas are determined important fordeveloping new medical treatments.Key Words : caspase, apoptosis, inhibitors of caspase, cis-platin