Previous studies suggest that dietary polyphenols and(or) their metabolites can exert beneficial effects against breast cancer. We usually consume in the diet, methylxanthines (caffeine, theobromine, etc.), with stimulant and cardioprotective properties, among others. However, it is unknown whether polyphenols can reach human malignant breast tumors in molecular forms and(or) at concentrations likely to act against cancer.
In this study, a controlled and randomized dietary intervention was conducted in breast cancer patients. The patients consumed three capsules daily containing resveratrol plus plant extracts (pomegranate, orange, lemon, olive, cocoa, and grape) from biopsy-confirmed diagnosis to surgery. The day of the surgery, urine, plasma, normal mammary tissue (NT), and malignant mammary tissue (MT) were collected. Samples were analyzed with ultra-high resolution liquid chromatography coupled to quadrupole time-of-flight mass spectrometry using a targeted metabolomics approach. We also evaluated possible antiproliferative and estrogenic/antiestrogenic activities in vitro, in breast cancer cells (MCF-7 and MDA-MB-231). We identified 101 metabolites in urine, 69 in plasma, 39 in NT, and 33 in MT. The vast majority of metabolites were conjugated. 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. Our results can be useful for the design of mechanistic studies on the effects of phenolic-derived metabolites that reach the mammary tissue.
Ávila-Gálvez, M.A.,1 García-Villalba, R.,1 Martínez-Díaz, F.,2 Ocaña-Castillo, B.,2 Monedero-Saiz, T.,1 Torrecillas-Sánchez, A.,3 Abellán, B.,4 González-Sarrías, A.,1 and Espín, J.C.1. Metabolic Profiling of Dietary Polyphenols and Methylxanthines in Normal and Malignant Mammary Tissues from Breast Cancer Patients. Mol. Nutr. Food Res. 2019, 63(9):e1801239.
1Laboratory of Food & Health, Research Group on Quality, Safety and Bioactivity of Plant Foods, CEBAS-CSIC, 30100 Campus de Espinardo, Murcia, Spain;
2-4Reina Sofía University Hospital (Services of 2Anatomical Pathology, 3Breast Unit and 4Surgery), Avda. Intendente Jorge Palacios s/n, 30003 Murcia, Spain.