Phase-II metabolism limits the antiproliferative activity of urolithins in human colon cancer cells

González‐Sarrías, Antonio; Giménez‐Bastida, Juan Antonio; Núñez‐Sánchez, María Ángeles; Larrosa, Mar; Garcı́a-Conesa, María Teresa; Tomás-Barberán, Francisco A.; Espı́n, Juan Carlos

doi:10.1007/s00394-013-0589-4

Cited by 108 publications

(107 citation statements)

References 40 publications

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“…The concentration of 40 µM UA was chosen because it is in the order of low micromolar levels, similar to what can be found in plasma after consumption of ET-rich foods [16,17,32] and was not cytotoxic to LNCaP cells [22]. In addition, most of the biological [18,31,33]. In our approach with cultured cells, a single dose of the minimum concentration of UA in order to see a transcriptional effect was used.…”

Section: Discussionmentioning

confidence: 99%

Urolithin A causes p21 up-regulation in prostate cancer cells

et al. 2015

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Section: Discussionmentioning

confidence: 99%

Urolithin A causes p21 up-regulation in prostate cancer cells

et al. 2015

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“…Plants rich in ellagitannins may prevent or delay the lengthy carcinogenesis process ]. Ellagitannins and ellagic acid inhibit cancers of the mouth, esophagus, lung, breast, liver and colon [Aqil et al 2012, González-Sarrías et al 2013a, b, Sakagami et al 2000, Wang et al 2010, 2013.…”

Section: Antitumor Activity Of Ellagitanninsmentioning

confidence: 99%

The structure, occurrence and biological activity of ellagitannins: a general review

Lipińska

Klewicka

Sójka

2014

Acta Sci Pol Technol Aliment

149

105

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The present paper deals with the structure, occurrence and biological activity of ellagitannins. Ellagitannins belong to the class of hydrolysable tannins, they are esters of hexahydroxydiphenoic acid and monosaccharide (most commonly glucose). Ellagitannins are slowly hydrolysed in the digestive tract, releasing the ellagic acid molecule. Their chemical structure determines physical and chemical properties and biological activity. Ellagitannins occur naturally in some fruits (pomegranate, strawberry, blackberry, raspberry), nuts (walnuts, almonds), and seeds. They form a diverse group of bioactive polyphenols with anti-infl ammatory, anticancer, antioxidant and antimicrobial (antibacterial, antifungal and antiviral) activity. Furthermore, they improve the health of blood vessels. The paper discusses the metabolism and bioavailability of ellagitannins and ellagic acid. Ellagitannins are metabolized in the gastrointestinal tract by intestinal microbiota. They are stable in the stomach and undergo neither hydrolysis to free ellagic acid nor degradation. In turn, ellagic acid can be absorbed in the stomach. This paper shows the role of cancer cell lines in the studies of ellagitannins and ellagic acid metabolism. The biological activity of these compounds is broad and thus the focus is on their antimicrobial, anti-infl ammatory and antitumor properties. Ellagitannins exhibit antimicrobial activity against fungi, viruses, and importantly, bacteria, including antibiotic-resistant strains such as methicillinresistant Staphylococcus aureus.

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“…3 Therefore, the development of new clinical treatments to overcome the resistance to conventional chemotherapy drugs such as 5-FU is urgently needed. 9,10 In the last few years, a wide range of biological activities of urolithins, mainly attributed to Uro-A, such as anticancer, 8,10,[15][16][17][18][19] anti-inflammatory, [20][21][22] and estrogenic/anti-estrogenic activities have been reported. 4,5 In particular, ellagitannins, polyphenols found in pomegranates, strawberries, raspberries, walnuts, and oak-aged wines, 6 are hydrolyzable tannins which release ellagic acid upon hydrolysis.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2015

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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.

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Phase-II metabolism limits the antiproliferative activity of urolithins in human colon cancer cells

Cited by 108 publications

References 40 publications

Urolithin A causes p21 up-regulation in prostate cancer cells

Urolithin A causes p21 up-regulation in prostate cancer cells

The structure, occurrence and biological activity of ellagitannins: a general review

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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