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Title: Inhibition of tumor growth by indole-3-carbinol in a prostate cancer xenograft model may be associated with disrupted gut microbial interactions

Author
item WU, YANBEI - Sichuan University
item Li, Robert
item HUANG, HAIQIU - University Of Maryland
item FLETCHER, ARNETTA - University Of Maryland
item YU, LU - University Of Maryland
item Pham, Quynhchi
item YU, LIANGLI - University Of Maryland
item HE, QIANG - Sichuan University
item Wang, Thomas - Tom

Submitted to: Nutrients
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/19/2019
Publication Date: 2/22/2019
Citation: Wu, Y., Li, R.W., Huang, H., Fletcher, A., Yu, L., Pham, Q., Yu, L., He, Q., Wang, T.T. 2019. Inhibition of tumor growth by indole-3-carbinol in a prostate cancer xenograft model may be associated with disrupted gut microbial interactions. Nutrients. 11(2). pii.E467. https://doi.org/10.3390/nu11020467.
DOI: https://doi.org/10.3390/nu11020467

Interpretive Summary: Prostate cancer is the most frequently diagnosed cancer and the second leading cause of cancer death in U.S. men. Accumulated evidence suggests that the cruciferous vegetables derived cancer protective compound indole-3-carbinol (I3C) may protect against prostate cancer, but the precise mechanisms underlying its action remain unclear. In this study, we tested the hypothesis that the beneficial effect of I3C may be due to the modulatory effect of the gut microbiome using a human prostate cancer cell (LNCaP) xenograft model. Athymic nude mice (5-7 weeks old, male, Balb c/c nu/nu) with established tumor xenografts were fed a basal diet (AIN-93) with or without 1 µmoles I3C/g for 9 weeks. The effect of I3C on gut microbial composition and microbial species interactions were then examined by 16s rRNA gene-based sequencing and co-occurrence network analysis. Our data show that I3C supplementation significantly inhibited tumor growth and altered the structure of gut microbiome. The abundance of the phylum Deferribacteres, more specifically, Mucispirillum schaedleri, was significantly increased by I3C. In addition, I3C consumption also changed gut microbial co-occurrence patterns. One of the network modules in the control group, consisting of 7 bacteria in family S-27, was positively correlated with tumor size (P<0.009). Moreover, I3C disrupted microbial interactions and altered this association between specific microbial network and tumor development. Our results unraveled complex relationships among I3C ingestion, gut microbiota, and prostate tumor development and may provide a novel insight into the mechanism for the chemopreventive effect of I3C on prostate cancer. This study provides novel information on the relationship between dietary compound, gut microbiome and prostate cancer development. The information will benefit basic and translational scientists who are studying the regulation of gut microbiome by diet and its effect on prostate cancer development.

Technical Abstract: Prostate cancer is the most frequently diagnosed cancer and the second leading cause of cancer death in U.S. men. Accumulated evidence suggests the cruciferous vegetables derived cancer protective compound indole-3-carbinol (I3C) may protect against prostate cancer but the precise mechanisms underlying its action remain unclear. In this study, we tested the hypothesis that the beneficial effect of I3C may be due to its modulatory effect on the gut microbiome using a human prostate cancer cell (LNCaP) xenograft model. Athymic nude mice (5-7 weeks old, male, Balb c/c nu/nu) with established tumor xenografts were fed a basal diet (AIN-93) with or without 1 µmoles I3C/ g for 9 weeks. The effect of I3C on gut microbial composition and microbial species interactions were then examined by 16s rRNA gene-based sequencing and co-occurrence network analysis. Our data show that I3C supplementation significantly inhibited tumor growth and altered the structure of gut microbiome. The abundance of the phylum Deferribacteres, more specifically, Mucispirillum schaedleri, was significantly increased by I3C. In addition, I3C consumption also changed gut microbial co-occurrence patterns. One of the network modules in the control group, consisting of 7 bacteria in family S-27, was positively correlated with tumor size (P<0.009). Moreover, I3C disrupted microbial interactions and altered this association between specific microbial network and tumor development. Our results unraveled complex relationships among I3C ingestion, gut microbiota, and prostate tumor development and may provide a novel insight into the mechanism for the chemopreventive effect of I3C on prostate cancer. This study provides novel information on the relationship between dietary compound, gut microbiome and prostate cancer development. The information will benefit basic and translational scientists who are studying the regulation of gut microbiome by diet and its effect on prostate cancer development.