NDLI: The ellagic acid-derived gut microbiota metabolite, urolithin A, potentiates the anticancer effects of 5-fluorouracil chemotherapy on human colon cancer cells

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The ellagic acid-derived gut microbiota metabolite, urolithin A, potentiates the anticancer effects of 5-fluorouracil chemotherapy on human colon cancer cells

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Food & Function Vol - 6 Issue - 4

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The ellagic acid-derived gut microbiota metabolite, urolithin A, potentiates the anticancer effects of 5-fluorouracil chemotherapy on human colon cancer cells

Content Provider	Royal Society of Chemistry (RSC)
Author	Espín, Juan Carlos Bellesia, Andrea Tomé-Carneiro, Joao Tomás-Barberán, Francisco A. González-Sarrías, Antonio
Copyright Year	2015
Abstract	Chemotherapy increases the overall survival in colorectal cancer (CRC) patients. 5-Fluorouracil (5-FU) remains as a drug of first choice in CRC therapy over the last four decades. However, only 10–15% of patients with advanced CRC respond positively to 5-FU monotherapy. Therefore, new strategies to enhance the 5-FU effectiveness, overcome the tumor cell resistance and decrease the unspecific toxicity are critically needed. Urolithin A (Uro-A) is the main metabolite produced by the human gut microbiota from the dietary polyphenol ellagic acid. Uro-A targets the colonic mucosa of CRC patients, and preclinical studies have shown the anti-inflammatory and cancer chemopreventive activities of this metabolite. We evaluated here whether Uro-A, at concentrations achievable in the human colorectum, could sensitize colon cancer cells to 5-FU and 5′DFUR (a pro-drug intermediate of 5-FU). We found that both 5-FU and 5′DFUR arrested the cell cycle at the S phase by regulating cyclins A and B1 in the human colon cancer cells Caco-2, SW-480 and HT-29, and also triggered apoptosis through the activation of caspases 8 and 9. Co-treatments with Uro-A decreased IC50 values for both 5-FU and 5′DFUR and additionally arrested the cell cycle at the G2/M phase together with a slight increase in caspases 8 and 9 activation. Overall, we show that Uro-A potentiated the effects of both 5-FU and 5′DFUR on colon cancer cells. This suggests the need for lower 5-FU doses to achieve similar effects, which could reduce possible adverse effects. Further in vivo investigations are warranted to explore the possible role of Uro-A as a chemotherapy adjuvant.
Starting Page	1460
Ending Page	1469
Page Count	10
File Format	HTM / HTML PDF
ISSN	20426496
Volume Number	6
Issue Number	5
Journal	Food & Function
DOI	10.1039/c5fo00120j
Language	English
Publisher	Royal Society of Chemistry
Access Restriction	Open
Subject Keyword	CRC Chemotherapy Colorectal cancer Fluorouracil Urolithin Metabolite Microbiota Polyphenol Acid Gastrointestinal tract Cancer Sensitize (That Petrol Emotion song) Cell cycle S phase Caco-2 Apoptosis IC50 Adjuvant
Content Type	Text
Resource Type	Article
Subject	Medicine Food Science

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Potential of the ellagic acid-derived gut microbiota metabolite - Urolithin A in gastrointestinal protection.

Postoperative Probiotics Administration Attenuates Gastrointestinal Complications and Gut Microbiota Dysbiosis Caused by Chemotherapy in Colorectal Cancer Patients.

Editorial: Gut microbiota and chemotherapy resistance of colorectal cancer

Antiproliferative activity of the ellagic acid-derived gut microbiota isourolithin A and comparison with its urolithin A isomer: the role of cell metabolism

Novel Regioselective Synthesis of Urolithin Glucuronides─Human Gut Microbiota Cometabolites of Ellagitannins and Ellagic Acid.

Gastrointestinal Simulation Model TWIN-SHIME Shows Differences between Human Urolithin-Metabotypes in Gut Microbiota Composition, Pomegranate Polyphenol Metabolism, and Transport along the Intestinal Tract.

The human gut microbial ecology associated with overweight and obesity determines ellagic acid metabolism

Description of urolithin production capacity from ellagic acid of two human intestinal Gordonibacter species

Gut Bacteria Involved in Ellagic Acid Metabolism To Yield Human Urolithin Metabotypes Revealed.

The ellagic acid-derived gut microbiota metabolite, urolithin A, potentiates the anticancer effects of 5-fluorouracil chemotherapy on human colon cancer cells

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Antiproliferative activity of the ellagic acid-derived gut microbiota isourolithin A and comparison with its urolithin A isomer: the role of cell metabolism

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Description of urolithin production capacity from ellagic acid of two human intestinal Gordonibacter species

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The ellagic acid-derived gut microbiota metabolite, urolithin A, potentiates the anticancer effects of 5-fluorouracil chemotherapy on human colon cancer cells