An article published online on July 28, 2009 in the Journal of the National Cancer Institute reported the discovery of researchers at Northwestern University in Chicago of the target for the soy isoflavone genistein in preventing the spread of prostate cancer.
Epidemiological studies have associated increased genistein intake with a reduction in metastatic prostate cancer rates. Although genistein has been shown to block the activation of a proinvasion pathway known as p38 mitogen-activated protein kinase (MAPK), genistein’s specific upstream target for inhibiting cell invasion had been unknown.
Previous research demonstrated that p38 MAPK increases matrix metalloproteinase-2 (MMP-2) expression and cell invasion. Matrix metalloproteinase-2 has been found to be elevated in invasive prostate cancer tissue. Using six prostate cell lines, Li Xu, MD, PhD, and Raymond C. Bergan, MD, of Northwestern’s Department of Medicine and their associates found that genistein binds to the active site of a protein upstream from p38 MAPK known as mitogen-activated protein kinase 4 (MEK4), which, when overexpressed, increased matrix metalloproteinase-2 expression and cell invasion in all lines. Enzymatic assay confirmed MEK4 activity inhibition by genistein.
In a randomized trial of 24 prostate cancer patients, matrix metalloproteinase-2 levels in normal prostate epithelial cells were found to be lower in genistein-treated patients than in those who did not receive genistein. “We showed, to our knowledge for the first time, that genistein treatment, compared with no treatment, was associated with decreased levels of matrix metalloproteinase-2 transcripts in normal prostate cells from prostate cancer-containing tissue,” the authors write. “This finding supports the possibility that destabilization of a premalignant field can potentially be prevented by therapeutically targeting cell motility processes that are linked to cancer, as has been proposed previously.”
—D Dye
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