Effects of genistein on invasion and matrix metalloproteinase activities of HT1080 human fibrosarcoma cells.
Effects of genistein on invasion and matrix metalloproteinase activities were investigated in HT1080 human sarcoma cells. Invasion of HT1080 cells through reconstituted basement membrane was inhibited when the cells were treated with 100 micromol/L and 200 micromol/L genistein. At the same concentrations, genistein not only suppressed latent forms of matrix metalloproteinase-2 and -9 (MMP-2 and MMP-9) to convert into active forms, but also increase dramatically the tissue inhibitor of metalloproteinase (TIMP-1) mRNA contents and reverse the imbalance of MMPs and TIMPs. However, expressions of MMP-2 and MMP-9 were not significantly affected. Suppression of MMP activation and increase of TIMP-1 expression will decrease matrix degradation by MMPs, and consequently inhibit invasions of the cells. These results emphasized the existence of the imbalance between MMPs and TIMPs in tumor invasion and metastasis formation. The value of genistein as a drug for antiinvasion and anti-metastasis chemotherapy was suggested.
Yan
C
C
Institute of Materia Medica, CAMS & PUMC, Beijing 100050.
Han
R
R
D000970:Antineoplastic Agents / Q000494:pharmacology; D005354:Fibrosarcoma / Q000378:metabolism / Q000473:pathology*; D019833:Genistein / Q000494:pharmacology*; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D012333:RNA, Messenger / Q000096:biosynthesis; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000096:biosynthesis* / Q000235:genetics; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; D019833:Genistein; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9