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

Abstract

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. Here, their metabolic profiling in normal (NT) and malignant (MT) mammary tissues of newly-diagnosed BC patients and the tissue-occurring metabolites' anticancer activity are evaluated. Patients (n = 26) consumed 3 capsules/day (turmeric, red clover, and flaxseed extracts plus resveratrol; 296.4mg phenolics/capsule) from biopsy-confirmed diagnosis to surgery (5±2 days) or did not consume capsules (n = 13). NT and MT, blood, and urine are 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±2.4µmolL-1 in NT and MT, respectively. Free curcumin, but not its glucuronide, was detected in the tissues (1.1±1.8 and 0.2±0.2µmolL-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. Curcuminoids could be coadjuvants that might help fight BC upon regular consumption.