Disposition of Dietary Polyphenols in Breast Cancer Patients' Tumors, and Their Associated Anticancer Activity: The Particular Case of Curcumin.

Scope Some polyphenol-derived metabolites reach human breast cancer (BC) tissues at concentrations that induce cell senescence. However, this is unknown for isoflavones, curcuminoids, and lignans. We evaluated here their metabolic profiling in normal (NT) and malignant (MT) mammary tissues of newly-diagnosed BC patients and explored the tissue-occurring metabolites' anticancer activity. Methods and results Patients (n = 26) consumed 3 capsules/day (turmeric, red clover, and flaxseed extracts plus resveratrol; 296.4 mg phenolics/capsule) from biopsy-confirmed diagnosis to surgery (5±2 days) or did not consume capsules (n = 13). NT and MT, blood, and urine were analyzed by UPLC-QTOF-MS using targeted metabolomics. Anticancer activity was tested in MCF-7 and MDA-MB-231 BC cells. Mainly phase-II metabolites were detected (108, 84, 49, and 47 in urine, plasma, NT, and MT, respectively). Total metabolite concentrations reached 10.7±11.1 and 2.5±2.4 μmol L-1 in NT and MT, respectively. Free curcumin, but not its glucuronide, was detected in the tissues (1.1±1.8 and 0.2±0.2 μmol L-1 in NT and MT, respectively). Breast tissue-occurring metabolites' antiproliferation was mainly exerted in p53-wild-type MCF-7 cells by curcuminoids through cell cycle arrest, senescence, and apoptosis induction via p53/p21 induction, while isoflavone-derived metabolites exerted estrogenic-like activity. Conclusion Curcuminoids could be coadjuvants that might help fight BC upon regular consumption. This article is protected by copyright. All rights reserved.