Effects of genistein and 2-methoxyestradiol on matrix metalloproteinases and their inhibitors secreted by Ehrlich ascites tumor cells

Background. Ehrlich ascites tumor is an experimental tumor model very suita ble for performing comparative studies relating its growth in vitro and in vivo. We used this armor model to study the potential modulatory effects of genistein and 2-methoxyestradiol, two anti-angiogenic compounds, on the pr oteolytic balance MMP/TIMP. Ehrlich cells grown in vitro secreted MMP-9, MM P-2 and two TIMPs; the treatment with either of the anti-angiogenic compoun ds here tested stimulated all these activities, but the increase in TIMPs a ctivities of genistein-treated cells were higher than those of MMPs, thus i nducing a decrease in the proteolytic balance. On the other hand, Ehrlich c ells growing in vivo did not produce any detectable TIMP activity, brit acc umulated MMP-9 and MMP-2 during tumor growth. Both compounds induced signif icant decrease of MMPs activity when tumor cells were actively proliferatin g. It was concluded that both genistein and 2-methoxyestradiol could shift the proteolytic balance MMP/TIMP towards antiproteolysis in media ol asciti c fluid conditioned by actively growing Ehrlich cells.