Investigation of cytotoxic and antiangiogenic effects of amiodarone and trastuzumab combination on breast cancer cells

In neoplastic progression, ion channels also contribute to the distinctive features of cancer, such as insensitivity to growth-inhibiting signals, invasion and metastasis, angiogenesis, and escape from apoptosis. Functions and properties of ion channels can change under pathological conditions. Some of these altered functions play a role in critical events for cancer cells such as survival and metastasis. Ion channels control cancer cell proliferation by regulating some important survival signaling pathways and membrane potential. However, there is no drug specifically designed to target ion channels for cancer treatment yet. Over time, drug forms have been developed to target ion channels, which are known to play a role in the pathophysiology of various diseases, and to treat these diseases. Many antiepileptic and migraine drugs, local anesthetics, antipsychotics, antiarrhythmics, antihypertensives and oral hypoglycemic agents can be counted among those used in these treatments. These clinically approved drugs can be reused for cancer treatment because of their convenience in time, known safety profile, agreed-upon pharmacokinetic mechanism and economic aspects. In this thesis study, the cytotoxic and antiangiogenic properties of trastuzumab, amiodarone alone and their combinations were investigated in MCF-7, MDA-MB-231, MCF-10A and HUVEC cell lines. Amiodarone, MCF-7 showed a statistically significant cytotoxic effect in MCF-7 cells at doses of 150, 100, 80, 60, 40, 20 µg/ml at the end of the incubation period of 48 hours. 72 hour incubation period, it showed a statistically significant cytotoxic effect on MCF-7 cells at doses of 150, 100, 80, 60, 40, 20, 10 µg/ml. 24, 48 and 72 hours incubation period, it showed a statistically significant cytotoxic effect on MDA-MB-231 cells at doses of 150, 100, 80, 60, 40, 20, 10 µg/ml. Trastuzumab did not show statistically significant cytotoxic effects in any cell line at 150, 100, 80, 60, 40, 20, 10, 5, 2.5 and 1 µg/ml doses. However, at the end of the 72 hour incubation period, it caused an antiproliferative effect in the dose range of 150-100 µg / ml. In combinations of amiodarone 1, 2.5 and 5 µg / ml in MCF-7 cells, no statistically significant cytotoxic effect is observed at any dose and causes a statistical decrease in cell viability. As a result of the data obtained, there is no statistically significant change in the amount of caspase-3 in MDA-MB-231 and MCF7 cells. In the results, it was observed that there was no apoptotic effect of the drugs alone or in combination, while a statistically significant decrease was observed in the amount of VEGF in MCF-7, MDA-MB-231, MCF10A and HUVEC cell lines at the end of the 24-hour incubation period with 2.5 µg / ml amiodarone, 5 µg / ml trastuzumab and their combinations.