Homocysteine is a potent inhibitor of human tumor cell gelatinases.
Extracellular matrix-degrading gelatinases are mainly involved in tumor invasion and metastasis. Previous experimental data from our group and others suggested that homocysteine could have a potential modulatory role on the proteolytic balance at the extracellular matrix. Therefore, we studied the effects of homocysteine on extracellular matrix-degrading proteases using model human tumor cell lines and a combination of in vitro fluorogenic assay and zymographic techniques. Homocysteine is shown to be the thiol compound with the most potent inhibitory activity on matrix metalloproteinase 9. Zymographies reveal that matrix metalloproteinase 2 is, at least, as sensitive to inhibition by homocysteine as matrix metalloproteinase 9 is. This study opens new ways to the potential pharmacological use of thiol compounds.
Chavarría
Teresa
T
Department of Molecular Biology and Biochemistry, Faculty of Sciences, University of Málaga, E-29071 Málaga, Spain.
Rodríguez-Nieto
Salvador
S
Sánchez-Jiménez
Francisca
F
Quesada
Ana R
AR
Medina
Miguel A
MA
D017077:Culture Media, Conditioned; D006710:Homocysteine / Q000494:pharmacology*; D006801:Humans; D061965:Matrix Metalloproteinase Inhibitors; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D011480:Protease Inhibitors / Q000494:pharmacology*; D013438:Sulfhydryl Compounds / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D017077:Culture Media, Conditioned; D061965:Matrix Metalloproteinase Inhibitors; D011480:Protease Inhibitors; D013438:Sulfhydryl Compounds; D006710:Homocysteine