Influence of Genistein Isoflavone on Matrix Metalloproteinase-2 Expression in Prostate Cancer Cells

Abstract

We investigated the expression of matrix metalloproteinase (MMP)-2 in human LNCaP and PC3 prostate cancer cell lines in response to genistein exposure. Initially we studied the phytosensitivity of the cells to genistein using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay to determine percentage cell viability/inhibition and the terminal deoxynucleotidyl transferase-mediated fluorescein-dUTP nick end-labeling apoptosis assay to assess the type of cell death. The results revealed that genistein inhibited growth and proliferation in both PC3 (hormone-dependent) and LNCaP (hormone-independent) prostate cancer cell lines, that there was no significant difference in sensitivity to genistein between PC3 and LNCaP cells, and that the effect of genistein on the cells was dose- and time-dependent. The results also revealed that inhibition of cell growth in both PC3 and LNCaP cells was predominantly due to apoptotic cell death. These results were consistent with data in previous studies. This was followed by determination of the MMP-2 profile in response to genistein treatment. The results indicated a significant dose- and time-dependent inhibition of MMP-2 expression levels in both cells, with a highly significant negative correlation between MMP-2 levels and concentration of genistein. This is of phytotherapeutic significance in view of the pivotal role of MMP-2 expression in the pathogenesis of prostate cancer. Increasing expression of MMPs has been identified in many human cancers, including prostate cancer. Our findings indicate that genistein could be a potent therapeutic inhibitor of MMP-2 in line with current concepts of targeted treatment.