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 suitable 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 proteolytic balance MMP/TIMP. Ehrlich cells grown in vitro secreted MMP-9, MMP-2 and two TIMPs; the treatment with either of the anti-angiogenic compounds here tested stimulated all these activities, but the increase in TIMPs activities of genistein-treated cells were higher than those of MMPs, thus inducing a decrease in the proteolytic balance. On the other hand, Ehrlich cells growing in vivo did not produce any detectable TIMP activity, brit accumulated MMP-9 and MMP-2 during tumor growth. Both compounds induced significant decrease of MMPs activity when tumor cells were actively proliferating. It was concluded that both genistein and 2-methoxyestradiol could shift the proteolytic balance MMP/TIMP towards antiproteolysis in media ol ascitic fluid conditioned by actively growing Ehrlich cells.