Effects of genistein and 2-methoxyestradiol on matrix metalloproteinases and their inhibitors secreted by Ehrlich ascites tumor cells.
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 tumor 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, but 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 or ascitic fluid conditioned by actively growing Ehrlich cells.
Departamento de Biología Molecular y Bioquímica, Facultad de Ciencias, Universidad de Málaga, Spain.
I
I
Fajardo
E
E
Díez
S
S
Rodríguez-Nieto
C
C
Rodríguez-Caso
A R
AR
Quesada
F
F
Sánchez-Jiménez
M A
MA
Medina
D000077584:2-Methoxyestradiol; D000818:Animals; D001202:Ascitic Fluid / Q000473:pathology; D002286:Carcinoma, Ehrlich Tumor / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D002448:Cell Adhesion / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology*; D019833:Genistein / Q000494:pharmacology*; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases / Q000378:metabolism; D051379:Mice; D010529:Peritoneal Cavity / Q000473:pathology; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism*
D004791:Enzyme Inhibitors; D061965:Matrix Metalloproteinase Inhibitors; D019714:Tissue Inhibitor of Metalloproteinases; D004958:Estradiol; D000077584:2-Methoxyestradiol; D019833:Genistein; D020782:Matrix Metalloproteinases