Cadmium inhibits gelatinolytic activities of MMP2 and MMP9: another possible mechanism of cadmium-induced carcinogenesis


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Livia Lacorte1, Carolina Sarobo1, Elaine Porto1, Luis Justulin Jr1, Flavia Delella1, Sergio Felisbino1
1Sao Paulo State University UNESP, Botucatu, SP, Brazil


Matrix Metalloproteinases are a set of neutral endopeptidases calcium and zinc-dependent. This family of enzymes plays a major role in the extracellular matrix components degradation and turnover in the most normal physiologic conditions and also in many diseases, such cancer. In this work, we evaluated the effect of cadmium, a divalent metal with known carcinogenic potential on prostate gland, on the MMP-2 and MMP-9 gelatinolytic activity.


For such, MMP-2 and MMP-9 extracted from normal rat ventral prostate were processed for gelatin zymography. The cadmium effect was tested during incubations step at different concentration (5mM, 2mM, 50uM and 1uM of Cadmium chloride) with or without 5mM of calcium chloride. The gels were incubated for 20 hours at 37ÂșC in a solution of 50mM pH 8.4 Tris-HCl containing the different concentration of cadmium and calcium described above.


The presence of cadmium chloride in the incubation buffer inhibited the gelatinolytic activity of both MMP-2 and MMP-9, even in the presence of calcium chloride. This result suggests that cadmium, such as magnesium, manganese and cobalt, has an inhibitory effect on MMP-2 and MMP-9 activity, in vitro.


Since cadmium can accumulate in the many organs, such as the prostate, we believe that inhibitory action of cadmium on MMPs activity may, at long term, participates in the process of carcinogenesis induced by cadmium. Further studies will address if prostates from cadmium-treated animals also present changes in MMP-2 and MMP-9 expression and activity.