The investigation of the effects of thalidomide an antiangiogenic and antitumoral drug, alone and in combination with radiotherapy on substance p level as well as substance p degrading enzymes; adam-10 and neprilysin in 4T1 VE 4THMpc mouse breast cancer cell lines

In this study, our aim was to investigate the effect of Thalidomide, known as antiangiogenic and antitumoral drug, alone or in combination with radiotherapy, on the amount of substance-P, an angiogenic factor, and on the substance-P degrading ADAM-10 and Neprilysin Enzyme Activities in 4T1 and 4THMpc mouse breast cancer cell lines. According to four different cytotoxicity test results, at the end of the 72 hour, 40 µg/ml thalidomide and 45 Gy Co60 irradiation alone showed significant cytotoxic effects on 4T1 and 4THMpc mouse breast cancer cell line. We demonstrate for the first time that at specified doses, thalidomide and irradiation together activates caspase-3, inhibits in vitro proliferation of 4T1 and 4THMpc breast cancer cells directly, potentiates the activity of ADAM 10 and Neprilysin enzymes. Moreover, as the result of changes in ADAM 10 and Neprilysin activity, measured SP levels were decreased when compared to the relative controls. We suggest that thalidomide and radiation together, lead hydrolysis of SP to its bioactive fragments and thus induce apoptosis. These data may provide the basis for strategies, in which it is possible to use thalidomide and irradiation together to enhance the apoptosis of tumor cells for improving the efficiancy of each independent therapy.