How Genistein Slows Metastasis in Prostate Cancer

Cancer researchers have shown how the antiprostate cancer isoflavone genistein functions at the molecular level to inhibit expression of genes that favor metastasis and spread of the disease.

Investigators from Northwestern University (Chicago, IL, USA) were particularly interested in the relationship between dietary genistein and the expression of the MEK4 (mitogen-activated protein kinase 4) gene. Toward this end, they worked with cultures of six different prostate cancer-cell lines. All the cell lines were transiently transfected with a MEK4 gene (to increase MEK4 expression), small interfering RNA against MEK4 (to decrease MEK4 expression), or corresponding control materials. Gene expression was assessed by a quantitative reverse transcription–polymerase chain reaction, and protein expression was determined by Western blot analysis. Cell invasion was assessed by a Boyden chamber assay.

Results published in the July 28, 2009, online edition of the Journal of the National Cancer Institute revealed that overexpression of MEK4 increased the expression of the MMP-2 (matrix metalloproteinase-2) gene, which has been linked to cell invasion. Decreased MEK4 expression had the opposite effects. Computer modeling indicated that genistein bound to the active site of MEK4, while an enzymatic assay showed that genistein inhibited MEK4 kinase activity. The expression of MMP-2 was significantly higher in normal prostate epithelial cells taken from untreated prostate cancer patients than they were in cells taken from genistein-treated patients.

Summarizing the results of the study, the authors said, "We have shown that it is possible to target motility-associated processes with genistein in patients with prostate cancer; have identified MEK4 as the therapeutic target for genistein in all six prostate cell lines examined; and have provided a possible mechanism to link high dietary consumption of genistein-containing foods with lower rates of prostate cancer metastasis and mortality.”

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