Regulation of steroid receptor expression and proliferation in prostate cancer by genistein and other flavonoids
J Bektic, R Guggenberger, G Schäfer, G Bartsch & H Klocker
A diet rich in phytoestrogens such as flavonoids has been attributed as one of the reasons for the low incidence of prostate cancer in Asia as opposed to Western countries with a diet rich in fat and meat and the highest incidences of this cancer. In many cellular models of prostate cancer these substances, the prototype of which is genistein, inhibit cell proliferation and cell cycle progression and enhance the rate of apoptosis. The molecular mechanisms involve modulation of steroid receptor expression and steroid hormone metabolism, inhibition of growth factor receptor and survival pathways and depend on concentration and cellular context. Prostate cells express high levels of estrogen receptors, estrogen receptor alpha being predominant in the stroma and estrogen receptor beta in the epithelium. Although the central hormonal regulation in the prostate is elicited through androgens, estrogens seem to play an important role as well and have been implicated in proliferative disorders of the prostate, e.g. cancer and benign hyperplasia. In the hormone-sensitive prostate cancer cell model LNCaP, genistein, an isoflavone downregulated androgen receptor protein expression thus abrogating the androgenic stimulation of growth and survival and expression and secretion of PSA. These cells express estrogen receptor beta and the effective concentrations as well as prevention of the genistein effect by estrogen receptor blockage indicated that the genistein effect was mediated via this estrogen receptor. Regulation of prostate growth involves interaction of different cell types and the prostatic stroma plays a crucial role as a paracrine stimulator. The flavonoid apigenin inhibited the proliferation and cell cycle progression of primary prostate stormal cells suggesting that phytoestrogen action on the prostate gland also involves the stromal compartment of the gland.