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

Authors: HUANG, HAIQIU - University Of Maryland; Pham, Quynhchi; YU, LIANGLI - University Of Maryland; Boue, Stephen; Wang, Thomas

Submitted to: Journal of Functional Foods
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/6/2024
Publication Date: 10/24/2024
Citation: Huang, H., Pham, Q., Yu, L., Boue, S.M., Wang, T.T. 2024. Differential preventative effect of soy-derived phytochemical glyceollins on prostate cancer in-vitro and in mouse tumor xenograft model. Journal of Functional Foods. 122. Article 106460. https://doi.org/10.1016/j.jff.2024.106460.
DOI: https://doi.org/10.1016/j.jff.2024.106460

Interpretive Summary: Prostate cancer remains a critical health problem in the US and the world. Prevention through consumption of a sound diet is an integral part of a concerted strategy to contain the mortality and minimize health burden for our society. However, the effect of diet on prostate cancer development remain unclear especially at the mechanisms level. The current study see to address this critical area. Glyceollins are soy-derived phytoalexins that have been proposed as candidate compounds for prostate cancer prevention. Our previous research had shown that glyceollins significantly inhibited the androgen-responsive Lymph Node Carcinoma of the Prostate (LNCaP) cell growth by regulating cell cycle and the androgen-mediated pathway. The present study aimed to extend the finding and to test the hypothesis that glyceollins can prevent prostate cancer in-vivo through modulation of the androgen-responsive pathway. We found dietary glyceollins attenuated LNCaP tumor xenograft growth in a nude mice model and correlated with inhibition of tumor cells proliferative marker PCNA mRNA levels. However, unlike in-vitro, dietary glyceollins did not affect marker genes for androgen responsive pathway, cell cycle, and angiogenesis in the tumor xenograft. Dietary glyceollins also did not affect marker genes for xenobiotic metabolism, cholesterol transport, and inflammatory pathway in liver. Glyceollins’ low bioavailability (0.054 ± 0.013 µM in the plasma) might have led to the lack of effectiveness on the marker genes in-vivo. Interestingly, dietary glyceollins led to significantly lower abundance of cecal Bifidobacterium as compared to the control diet. Thus, glyceollins act differently in-vitro and in-vivo and its protective effect in-vivo may be independent of the androgen responsive pathway. This study provide novel information on molecular regulation of prostate cancer by diet-derived bio-active components. The information will benefit basic and translational scientist working on research related to understanding interaction between food, the gut microbiome. and prostate canncer prevention.

Technical Abstract: 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.