A comparative study of the effects of genistein and 2-methoxyestradiol on the proteolytic balance and tumour cell proliferation.
The cytotoxicity of two compounds described as anti-angiogenic, the isoflavone genistein and the oestrogen metabolite 2-methoxyestradiol, has been studied in different human tumour cell lines. Since the degradation of the extracellular matrix is one of the essential steps in angiogenesis, the potential modulatory effects of both compounds on the proteolytic balance in media conditioned by different human tumour cells have been also investigated. The IC50 values for 2-methoxyestradiol were lower than those for genistein on all the cell lines tested. In all the cell lines expressing measurable amounts of active enzymes, genistein induced a shift towards antiproteolysis in both matrix metalloproteinase/tissue inhibitor of metalloproteinase and urokinase/plasminogen activator inhibitor proteolytic balances. On the other hand, 2-methoxyestradiol did not produce any clear net shift of the proteolytic balance, with the significant exception of the matrix metalloproteinase/tissue inhibitor of metalloproteinase balance in WAC-2 cells, a neuroblastoma cell line with enhanced expression of the N-myc oncogene.
Fajardo
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I
Laboratorio de Bioquímica y Biología Molecular, Facultad de Ciencias, Universidad de Málaga, Spain.
Quesada
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AR
Núñez de Castro
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Sánchez-Jiménez
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Medina
M A
MA
D000077584:2-Methoxyestradiol; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D017364:Collagenases / Q000502:physiology; D017077:Culture Media, Conditioned; D010450:Endopeptidases / Q000187:drug effects / Q000502:physiology*; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology; D016326:Extracellular Matrix Proteins / Q000187:drug effects* / Q000502:physiology; D018093:Gelatinases / Q000502:physiology; D019833:Genistein / Q000494:pharmacology*; D006801:Humans; D020778:Matrix Metalloproteinase 2; D019278:Matrix Metalloproteinase 3 / Q000502:physiology; D020780:Matrix Metalloproteinase 9; D008666:Metalloendopeptidases / Q000502:physiology; D010447:Peptide Hydrolases / Q000494:pharmacology*; D015849:Plasminogen Inactivators / Q000502:physiology; D011480:Protease Inhibitors / Q000494:pharmacology*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D019714:Tissue Inhibitor of Metalloproteinases / Q000502:physiology; D014407:Tumor Cells, Cultured; D014568:Urokinase-Type Plasminogen Activator / Q000502:physiology
D000970:Antineoplastic Agents; D017077:Culture Media, Conditioned; D016326:Extracellular Matrix Proteins; D015849:Plasminogen Inactivators; D011480:Protease Inhibitors; D019714:Tissue Inhibitor of Metalloproteinases; D004958:Estradiol; D000077584:2-Methoxyestradiol; D019833:Genistein; D011505:Protein-Tyrosine Kinases; D010450:Endopeptidases; D010447:Peptide Hydrolases; D014568:Urokinase-Type Plasminogen Activator; D017364:Collagenases; D018093:Gelatinases; D008666:Metalloendopeptidases; D019278:Matrix Metalloproteinase 3; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9