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

在 3D HCT116 球体上筛选天然(多)酚和肠道相关代谢物,揭示了黄烷-3-醇代谢物的肠道健康益处

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作者:Josep Rubert, Pamela Gatto, Michael Pancher, Viktoryia Sidarovich, Claudio Curti, Pedro Mena, Daniele Del Rio, Alessandro Quattrone, Fulvio Mattivi0

Conclusion

A chronic exposure to (4R)-5-(3',4'-dihydroxyphenyl)-γ-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.

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, µM concentration levels of (4R)-5-(3',4'-dihydroxyphenyl)-γ-valerolactone significantly decrease spheroid size at early stages of spheroid aggregation and gene expression of matrix metalloproteinases.

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