Publication: Metabolic profiling of dietary polyphenols and methylxanthines in normal and malignant mammary tissues from breast cancer patients
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Date
2019-02-04
Authors
Ávila-Gálvez, María Ángeles ; García-Villalba, Rocío ; Martínez Díaz, Francisco ; Ocaña-Castillo, Beatriz ; Monedero-Saiz, Tamara ; Torrecillas-Sánchez, Adela ; Abellán, Beatriz ; González Sarrías, Antonio ; Espín, Juan Carlos
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Publisher
Wiley, Wiley-VCH Verlag
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DOI
https://doi.org/10.1002/mnfr.201801239
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info:eu-repo/semantics/article
Description
© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. This document is the Published version of a Published Work that appeared in final form in Molecular Nutrition & Food Research. To access the final edited and published work see https://doi.org/ 10.1002/mnfr.201801239
Abstract
Scope: Dietary polyphenols may protect against breast cancer. However, it is unknown whether polyphenols reach human malignant breast tumors in molecular forms and(or) at concentrations likely to act against cancer.
Methods and Results: Ninteen breast cancer patients consumed three capsules daily from biopsy-confirmed diagnosis to surgery (6 ± 2 days). The capsules contained pomegranate, orange, lemon, olive, cocoa, and grapeseed extracts plus resveratrol, providing 37 different phenolics (473.7 mg), theobromine and caffeine (19.7 mg). A total of 101 metabolites are identified in urine, 69 in plasma, 39 in normal (NT), and 33 in malignant (MT) tissues by UPLC-ESI-QTOF-MS. Eight control patients did not consume extracts. Phenolic-derived metabolites in MT and NT are mainly glucuronidated and(or) sulfated. Some representative metabolites detected in MT (median and range, pmol g−1) are urolithin-A-3-O-glucuronide (26.2; 3.2−66.5), 2,5-dihydroxybenzoic acid (40.2; 27.7−52.2), resveratrol-3-O-sulfate (86.4; 7.8−224.4), dihydroresveratrol-3-O-glucuronide (109.9; 10.3−229.4), and theobromine (715.0; 153.9−3,216). Metabolites, as detected in breast tissues, do not exert antiproliferative or estrogenic/antiestrogenic activities in MCF-7 breast cancer cells.
Conclusion: This is the first study that describes the metabolic profiling of dietary phenolics and methylxanthines in MT and NT comprehensively. Although phase-II conjugation might hamper a direct anticancer activity, long-term tumor-senescent chemoprevention cannot be discarded.
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Citation
Mol. Nutr. Food Res. 2019, 63, 1801239
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