Antiproliferative and cytotoxic effects of captopril and losartan on A549, NIH3T3, RATEC and C6 cell cultures

Discovery of interfering drugs with renin-angiotensin system, such as captopril, losartan, etc., is a real breakthrough for the clinical management of hypertension and other life threatening cardiovascular diseases. Recently, beneficial effects captopril and losartan on various cancer types have been noticed during their clinical uses. In this context, they have been reported to possess antiproliferative and cytotoxic activities in various cancer patients. However, these antiproliferative and cytotoxic effects with captopril and losartan have been reported not only in clinical studies, but also in cell culture studies and in vivo investigations with tumor bearing animals. The present thesis studies were, therefore, designed for the investigation of antiproliferative and cytotoxic effects of captopril and losartan on certain malignant and non-malignant cell lines, A549 non-small cell lung adenocarcinoma cells, C6 glioma cells, NIH3T3 fibroblasts and RATEC endothelial cells. Within the scope of this study, it was aimed to investigate the antiproliferative and cytotoxic effects of captopril and losartan on A549 cells, C6 glioma cells, NIH3T3 fibroblasts and RATEC cells in relation to their nitric oxide production, which has been reported as an important endogenous factor for immune defense, angiogenesis and cytotoxicity against malignant cells. Among the cell lines used, C6 glioma cells and RATEC cells have not been investigated previously for the antiproliferative and cytotoxic effects of captopril and losartan or relatively less investigated only with a few previous studies. In addition, the effects of these two drugs on the proliferation abilities and nitric oxide productions of C6 glioma cells and RATEC cells have not been investigated previously. There is also a limited number of investigations related to the effects of captopril and losartan on A549. The findings obtained in the present study revealed that captopril and losartan have antiproliferative and cytotoxic effects whose potencies are varying from one cell type to another cell type. Similar situation was also observed in the nitric oxide production abilities of the cultured cells. The most probable reason for varying potencies observed in these experiments seem to be varying expressions of renin-angiotensin system components in cultured cells tested. Findings obtained in the present study were discussed on the basis of literature data. Keywords: captopril, losartan, antiproliferative effect, cytotoxicity, nitric oxide