Differential preventative effect of soy-derived phytochemical glyceollins on prostate cancer in-vitro and in mouse tumor xenograft is related to bioavailability of glyceollins and modulation of the gut microbiome

Glyceollins are soy-derived phytoalexins that have been proposed as candidate compounds for the prevention of prostate cancer. The present study tested the efficacies of glyceollins on prostate cancer prevention in-vitro and in-vivo. In-vitro, glyceollins significantly inhibited the androgen-responsive LNCaP cell growth consistent with inhibition of the androgen-mediated pathway. In-vivo, dietary glyceollins attenuated LNCaP tumor xenograft growth in a nude mouse model and correlated with the inhibition of tumor cells proliferative marker PCNA mRNA levels. However, unlike in-vitro, dietary glyceollins did not affect marker genes for the androgen- responsive pathway, cell cycle, and angiogenesis in the tumor xenograft. Dietary glyceollins also did not affect the marker genes for xenobiotic metabolism, cholesterol transport, or inflammatory pathways in liver. The low bioavailability of glyceollins (0.054 ± 0.013 µM in the plasma) might have led to the lack of effectiveness of glyceollins on the marker genes in-vivo. Interestingly, dietary glyceollins significantly lower the abundance of cecal Bifidobacterium, butyrate producing bacteria, compared to the control diet. Thus, glyceollins act differently in-vitro and in-vivo. The protective effects of glyceollins in-vivo may be independent of the androgen responsive pathway but related to modulation of the butyrate, a putative prostate cancer promoting agent, production by the gut microbiome.