Investigation of the cytotoxic effects of endostatin, vinorelbine and their combination of human endotelial, kidney epitelial and breast cancer cells

Classical cancer treatments known as surgical intervention, chemotherapy and radiotherapy are applied for over 40 years. Chemotherapy is a classic cancer treatment that targeted to destroy tumor cells directly by using cytotoxic or cytostatic effects of some chemicals.The agent in question is used to target tumor cells. However during the application of high doses of chemotherapy normal cells are also effected by theratment as well as cancer cells and occured as toxic side effects. In addition, depending on the agents used, cancer cells usually develop resistance against tested chemicals. Therefore success of the treatment gradually decreases. Chemotherapy is combined with different cancer treatments to increase the effectiveness of treatment and to reduce these toxic side effects.Endostatin is a 20 kDa endogenous anti-angiogenic factor that is derived from end of the C-terminal of collagen XVIII. Endostatin, inhibits endothelial cell migration, induces apoptosis and thereby it obstacles to create new tumor blood vessels from the existing tumor cells. Jing and colleagues combined a commercial and clinically used form of endostatin, endostar, with cisplatin, vinorelbine and paclitaxel. As a result of this study they showed a significant inhibition on the tumor size of non-small cell lung cancer cells due to the positive effects of the combinations.Vinorelbine is a semisynthetic substance obtained from Catharanthus roseus extract alkoloids. In 1994, the FDA (Federal Drug Administration) approved vinorelbine for the treatment of non-small cell lung cancers. Since then, it has been used in the treatment of non-small cell lung cancer, breast cancer and prostate cancer. As vinorelbine has little or no toxic side effects on normal cells, it has been widely used, either alone or in combinations, in various investigations. We think that to combined vinorelbine with an antiangiogenic agent will provide positive effects to reduce the amount of effective doses of both tested agents. Because of this reason; our aim of this study has been to determine the cytotoxic effects of endostatin and vinorelbine, either alone or in combination, in breast cancer cells. In addition, the effects of endostatin and vinorelbine combination on TNF-? and caspase-2,3,6,8 and 9 proteins which are known among the key apoptotic proteins had be exposed. Moreover cytotoxic effects of endostatin, vinorelbine and their combinations have also be studied in normal epithelial cells.By this study, for the first time, endostatin was combined with vinorelbine and results showed that endostatin caused a cytotoxic effect on cancer cells via TNF-? and caspase-8 pathways. The synergetic effects of endostatin and vinorelbin was shown at only certain doses.