Chemoprevention of Colorectal Cancer by Anthocyanidins and Mitigation of Metabolic Shifts Induced by Dysbiosis of the Gut Microbiome
| Autor: | Ashley M. Mudd, Radha Munagala, Jeyaprakash Jeyabalan, Ramesh C. Gupta, Tao Gu, Nejat K. Egilmez |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Cancer Research Carcinogenesis Cell Survival Colon Colorectal cancer Adenomatous Polyposis Coli Protein Vaccinium myrtillus Gut flora Exosomes Article Anthocyanins Bacteroides fragilis Mice 03 medical and health sciences 0302 clinical medicine Western blot Benzo(a)pyrene medicine Animals Humans Intestinal Mucosa Carcinogen chemistry.chemical_classification Drug Carriers medicine.diagnostic_test biology Cancer Neoplasms Experimental HCT116 Cells medicine.disease biology.organism_classification Microvesicles Gastrointestinal Microbiome Milk 030104 developmental biology Enzyme Liver Oncology chemistry Fruit 030220 oncology & carcinogenesis Colonic Neoplasms Carcinogens Cancer research Dysbiosis HT29 Cells |
| Zdroj: | Cancer Prev Res (Phila) |
| ISSN: | 1940-6215 1940-6207 |
| DOI: | 10.1158/1940-6207.capr-19-0362 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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