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Journal of Cancer Prevention

Original Article

J Cancer Prev 2022; 27(1): 50-57

Published online March 30, 2022

© Korean Society of Cancer Prevention

Protocatechuic Acid, a Gut Bacterial Metabolite of Black Raspberries, Inhibits Adenoma Development and Alters Gut Microbiome Profiles in ApcMin/+ Mice

Athena Dong1 , Chien-Wei Lin2 , Carla Elena Echeveste1 , Yi-Wen Huang3 , Kiyoko Oshima4 , Martha Yearsley5 , Xiao Chen1 , Jianhua Yu6,* , Li-Shu Wang1,*

1Division of Hematology and Oncology, Department of Medicine, Medical College of Wisconsin, 2Division of Biostatistics, Medical College of Wisconsin, 3Department of Obstetrics and Gynecology, Medical College of Wisconsin, Milwaukee, WI, 4Department of Pathology, Johns Hopkins University, Baltimore, MD, 5Department of Pathology, The Ohio State University, Columbus, OH, 6Department of Hematology & Hematopoietic Cell Transplantation, City of Hope National Medical Center and Beckman Research Institute, Duarte, CA, USA

Correspondence to :
Li-Shu Wang, E-mail:,
Jianhua Yu, E-mail:,
*These authors contributed equally to this work as co-correspondence authors.

Received: February 25, 2022; Revised: March 19, 2022; Accepted: March 21, 2022

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited.


Administration of black raspberries (BRBs) and their anthocyanin metabolites, including protocatechuic acid (PCA), has been demonstrated to exert chemopreventive effects against colorectal cancer through alteration of innate immune cell trafficking, modulation of metabolic and inflammatory pathways, etc. Previous research has shown that the gut microbiome is important in the effectiveness of chemoprevention of colorectal cancer. This study aimed to assess the potency of PCA versus BRB dietary administration for colorectal cancer prevention using an ApcMin/+ mouse model and determine how bacterial profiles change in response to PCA and BRBs. A control AIN-76A diet supplemented with 5% BRBs, 500 ppm PCA, or 1,000 ppm PCA was administered to ApcMin/+ mice. Changes in incidence, polyp number, and polyp size regarding adenomas of the small intestine and colon were assessed after completion of the diet regimen. There were significant decreases in adenoma development by dietary administration of PCA and BRBs in the small intestine and the 5% BRB-supplemented diet in the colon. Pro-inflammatory bacterial profiles were replaced with anti-inflammatory bacteria in all treatments, with the greatest effects in the 5% BRB and 500 ppm PCA-supplemented diets accompanied by decreased COX-2 and prostaglandin E2 levels in colonic mucosa. We further showed that 500 ppm PCA, but not 1,000 ppm PCA, increased IFN-γ and SMAD4 levels in primary cultured human natural killer cells. These results suggest that both BRBs and a lower dose PCA can benefit colorectal cancer patients by inhibiting the growth and proliferation of adenomas and promoting a more favorable gut microbiome condition.

Keywords: Colorectal neoplasms, Genes, APC, Rubus, Gastrointestinal microbiome


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