High consumption of soybean products, such as
phytoestrogens, has been hypothesized to contribute to a reduced incidence of
prostate cancer in Southeast Asian people, although there have been inconsistent results among studies. Human LNCaP cells, extensively used as a model for
androgen-dependent prostate
tumor, express the
androgen receptor (AR) mutant T877A promiscuously transactivated by
estrogens and other
ligands, which may further facilitate
cancer progression. Here, for the first time to our knowledge, we demonstrate that
genistein and
quercetin, two
phytoestrogens abundantly present in soybeans, activate either the AR mutant T877A in LNCaP or in transfected Chinese hamster ovary cells. This observation is supported by their capability to induce AR accumulation in the nuclear compartment of LNCaP together with
mRNA down-regulation of the
androgen target genes AR and PAP, and PSA up-regulation. Of interest, at concentrations eliciting transcriptional activity, both
genistein and
quercetin stimulate LNCaP cell growth, whereas at high levels, they become cytotoxic independently of AR expression, as ascertained in
steroid receptor-negative Hela cells. The results of our study provide evidence that
phytoestrogens may regulate several signaling processes in LNCaP cells; however, further studies are needed to assess their potential capability to restrain prostate
tumor progression.