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

Abstract

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. 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. 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 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 ± 2.4 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.

Targeting Mammalian 5-Lipoxygenase by Dietary Phenolics as an Anti-Inflammatory Mechanism: A Systematic Review

“…Under the same conditions, their free forms (quercetin, Uro-A, IsoUro-A, and Uro-C) effectively decreased 5-HETE, LTB 4 , PGE 2 , HKE 2 , and HKD 2 levels in a dose-dependent manner. Although the free forms are hardly found in the bloodstream, their presence in inflammatory environments is conceivable via deconjugation, as described for luteolin, quercetin, resveratrol, Uro-A, and curcumin [ 77 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 ].…”

“…The flavonoid glycoside rutin (quercetin-3-rutinoside) acts as a precursor (via deglycosylation) of quercetin in the colon [ 74 ], whereas curcumin and flavanones (such as the glycoside hesperidin and its aglycone hesperetin) can be detected in the colon for hours in their original form [ 75 , 76 ]. Upon absorption, the (poly)phenolic compounds and the microbial metabolites undergo phase-II metabolism to form conjugated molecules (glucuronides, sulfates, and methyl esters), which are the main molecules detected in the bloodstream, intestinal tissues, bile, feces, urine, and different systemic tissues [ 77 , 78 ]. Animal and human metabolism and bioavailability studies have reported that, at the intestinal level, the parental phenolic compounds (which serve as substrates of the gut microbiota) and their microbial-derived metabolites can achieve concentrations from μM to mM.…”

“…Interestingly, the increasing knowledge about the metabolism of these compounds indicates that, under inflammatory conditions, the circulating glucuronides might also play a role as precursors of their aglycones, including luteolin [ 83 , 84 ], quercetin [ 85 , 86 , 87 , 88 , 89 ], resveratrol [ 90 ], Uro-A [ 91 ], and curcumin [ 82 ]. Besides, a recent trial showed that the intake of a (poly)phenolic cocktail by breast cancer patients allowed detecting relevant concentrations of free curcumin, most likely due to a conjugation-saturation process, in malignant mammary tumors [ 77 ].…”

Comparison of the Effects of Resveratrol and Its Derivatives on the Radiation Response of MCF-7 Breast Cancer Cells

“…Orally administered resveratrol, like other polyphenols, has poor bioavailability and is converted into a wide variety of metabolites. Growing evidence highlights that mainly glucuronide and sulfate conjugates metabolites of resveratrol are the molecules that could reach systemic human tissues [69,70]. Ávila-Gálvez et al showed, that in normal and malignant mammary tissues from breast cancer patients major metabolites of resveratrol are resveratrol-3-O-sulfate and dihydro resveratrol-3-O-glucuronide.…”

Exploring the Biological Activity and Mechanism of Xenoestrogens and Phytoestrogens in Cancers: Emerging Methods and Concepts

“…In breast cancer cells and tissues exposed to CUR, it has been shown to decrease ER expression, leading to decreased cell proliferation, migration, invasion, and angiogenesis, while increasing apoptosis, cell cycle arrest, and senescence in breast cancer cell lines [93][94][95]. In clinical trials, CUR has been shown to slightly reduce fatigue in women with advanced, metastatic breast cancer and can be used as an anti-oxidation, anti-cancer agent that does not compromise the therapeutic efficacy of radiotherapy [96][97][98][99].…”