Chemoprevention of Colorectal Cancer by Anthocyanidins and Mitigation of Metabolic Shifts Induced by Dysbiosis of the Gut Microbiome
Authors: Ashley M Mudd
Jeyaprakash Jeyabalan
Ramesh C Gupta
Nejat K Egilmez
Radha Munagala
Tao Gu
Journal: Cancer Prevention Research (2020)
Discipline: CLINICAL MEDICINE
Keywords: Diets; fat; smoking; environmental pollutants; dysbiosis
Affiliations: Department of Pharmacology and Toxicology, University of Louisville, Louisville, Kentucky., Department of Microbiology and Immunology, University of Louisville, Louisville, Kentucky., James Graham Brown Cancer Center, University of Louisville, Louisville, Kentucky., Department of Medicine, University of Louisville, Louisville, Kentucky., Department of Pharmacology and Toxicology, University of Louisville, Louisville, Kentucky. .

Abstract:  Diets rich in fat, smoking, as well as exposure to environmental pollutants and dysbiosis of gut microbiota, increase the risk of developing colorectal cancer. Much progress has been made in combating colorectal cancer. However, options for chemoprevention from environmental insult and dysbiosis of gut microbiota remain elusive. We investigated the influence of berry-derived anthocyanidins (Anthos), with and without encapsulating them in bovine milk-derived exosomes (ExoAnthos), on the chemoprevention of bacteria-driven colon tumor development. Anthos and ExoAnthos treatment of colon cancer cells showed dose-dependent decreases in cell viability. Calculated selectivity index (SI) values for Anthos and ExoAnthos suggest that both treatments selectively targeted cancer over normal colon cells. In addition, ExoAnthos treatment yielded higher SI values than Anthos. Anthos and ExoAnthos treatment of ApcMin/+ mice inoculated with enterotoxigenic Bacteriodes fragilis (ETBF) bacteria led to significant decreases in colon tumor numbers over mice receiving vehicle treatments. Western blot analysis of normal colon, colon tumor, and liver tissue lysates showed that mice inoculated with ETBF featured increased expression of phase I enzymes in normal colon tissue and decreased expression of phase II enzymes in liver tissue. Treatment with the Anthos and ExoAnthos reverted the modulation of phase I and phase II enzymes, respectively; no significant changes in phase II enzyme expression occurred in colon tumor tissue. Treatment of HCT-116 cells with the ubiquitous carcinogen, benzo[a]pyrene (B[a]P) led to similar modulation of phase I and II enzymes, which was partially mitigated by treatment with Anthos. These results provide a promising outlook on the impact of berry Anthos for prevention and treatment of bacteria- and B[a]P-driven colorectal cancer. 

Retracted: No

PubPeer comments:
 Identified by another reader. *** ![file] , 
 Dr. Santosh Katiyar was the senior author on this paper and was the one involved in these experiments. He is the one who should be contacted as I was not involved in these data. , 
 https: retractionwatch.com 2019 01 07 former-uab-natural-products-researcher-up-to-a-dozen-retractions , 
 #2 Thank you for responding. As the senior author is no longer with his institution, is it possible for you or your other co-author to contact the journal to request they examine this concern? The repeated image seems self-evident. ,