Scope Epidemiological evidence suggests that a reduced risk of colorectal cancer (CRC) is correlated with high consumption of fruits and vegetables, which are major sources of fiber and phytochemicals, such as flavan-3-ols. However, it remains unknown how these phytochemicals and their specific gut-related metabolites may alter cancer cell behavior. Methods and results A focused screening using native (poly)phenols and gut microbial metabolites (GMMs) on 3D HCT116 spheroids is carried out using a high-throughput imaging approach. Dose-responses, IC50, and long-term exposure are calculated for the most promising native (poly)phenols and GMMs. As a result, this research shows that (poly)phenol catabolites may play a key role in preventing cancer propagation. Indeed, mu M concentration levels of (4R)-5-(3MODIFIER LETTER PRIME,4MODIFIER LETTER PRIME-dihydroxyphenyl)-gamma-valerolactone significantly decrease spheroid size at early stages of spheroid aggregation and gene expression of matrix metalloproteinases. Conclusion A chronic exposure to (4R)-5-(3MODIFIER LETTER PRIME,4MODIFIER LETTER PRIME-dihydroxyphenyl)-gamma-valerolactone may lead to a reduced CRC risk. Daily intake of monomeric, oligomeric, and polymeric flavan-3-ols may increase the colonic concentrations of this metabolite, and, in turn, this compound may act locally interacting with intestinal epithelial cells, precancerous and cancer cells.

A Screening of Native (Poly)phenols and Gut-Related Metabolites on 3D HCT116 Spheroids Reveals Gut Health Benefits of a Flavan-3-ol Metabolite / Rubert, Josep; Gatto, Pamela; Pancher, Michael; Sidarovich, Viktoryia; Curti, Claudio; Mena, Pedro; Del Rio, Daniele; Quattrone, Alessandro; Mattivi, Fulvio. - In: MOLECULAR NUTRITION & FOOD RESEARCH. - ISSN 1613-4125. - 66:21(2022), p. 2101043. [10.1002/mnfr.202101043]

A Screening of Native (Poly)phenols and Gut-Related Metabolites on 3D HCT116 Spheroids Reveals Gut Health Benefits of a Flavan-3-ol Metabolite

Rubert, Josep
;
Curti, Claudio;Mena, Pedro;Del Rio, Daniele;
2022

Abstract

Scope Epidemiological evidence suggests that a reduced risk of colorectal cancer (CRC) is correlated with high consumption of fruits and vegetables, which are major sources of fiber and phytochemicals, such as flavan-3-ols. However, it remains unknown how these phytochemicals and their specific gut-related metabolites may alter cancer cell behavior. Methods and results A focused screening using native (poly)phenols and gut microbial metabolites (GMMs) on 3D HCT116 spheroids is carried out using a high-throughput imaging approach. Dose-responses, IC50, and long-term exposure are calculated for the most promising native (poly)phenols and GMMs. As a result, this research shows that (poly)phenol catabolites may play a key role in preventing cancer propagation. Indeed, mu M concentration levels of (4R)-5-(3MODIFIER LETTER PRIME,4MODIFIER LETTER PRIME-dihydroxyphenyl)-gamma-valerolactone significantly decrease spheroid size at early stages of spheroid aggregation and gene expression of matrix metalloproteinases. Conclusion A chronic exposure to (4R)-5-(3MODIFIER LETTER PRIME,4MODIFIER LETTER PRIME-dihydroxyphenyl)-gamma-valerolactone may lead to a reduced CRC risk. Daily intake of monomeric, oligomeric, and polymeric flavan-3-ols may increase the colonic concentrations of this metabolite, and, in turn, this compound may act locally interacting with intestinal epithelial cells, precancerous and cancer cells.
A Screening of Native (Poly)phenols and Gut-Related Metabolites on 3D HCT116 Spheroids Reveals Gut Health Benefits of a Flavan-3-ol Metabolite / Rubert, Josep; Gatto, Pamela; Pancher, Michael; Sidarovich, Viktoryia; Curti, Claudio; Mena, Pedro; Del Rio, Daniele; Quattrone, Alessandro; Mattivi, Fulvio. - In: MOLECULAR NUTRITION & FOOD RESEARCH. - ISSN 1613-4125. - 66:21(2022), p. 2101043. [10.1002/mnfr.202101043]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11381/2933474
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