Research Article| Volume 55, SUPPLEMENT 1, S37-S46, November 01, 2006

The flavonoid apigenin inhibits the proliferation of prostatic stromal cells via the MAPK-pathway and cell-cycle arrest in G1/S



      Phytoestrogen apigenin, a member of flavonoids, has been described for its ability to induce growth arrest in carcinomas of colon, breast and prostate. In order to identify its influence on the prostatic stroma, which plays a crucial role in the pathogenesis of benign prostatic hyperplasia (BPH), we investigated the effect of apigenin on cell proliferation and cell-cycle progression.


      Prostatic stromal cells were isolated from nonmalignant tissue specimens obtained from patients undergoing radical prostatectomy. After incubation with increasing concentrations of apigenin for 24, 48 and 72 h the cell proliferation was determined by MTT assay. Cell-cycle regulation was examined by FACS analysis and the expression level of proteins involved in the G1/S transition was determined by immunoblot analysis.


      Apigenin treatment resulted in a significant inhibition of proliferation starting at a concentration of 30 μM of the flavonoid. FACS analysis showed cell-cycle arrest at a G1/S transition point. Furthermore, apigenin modified the expression levels of cell-cycle regulatory proteins leading to a dose-dependent decrease of cyclin D1 and an increase of p21/WAF1 expression, as determined by immunoblot analysis. As apigenin lead to a decrease of the phosphorylation status of ERK1 and 2, we postulated that the mechanism of apigenin action is mediated through mitogen activated kinases (MAPK)-pathway.


      Taken together, in response to apigenin treatment prostatic stromal cells showed a dose-dependent inhibition of cell proliferation, which may be due to a cell-cycle growth arrest and seems to occur via MAPK-pathway. These results suggest possible beneficial effects of apigenin in the prevention and/or treatment of benign prostatic hyperplasia.


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