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

• Published in: Molecular nutrition & food research Vol. 65; no. 12; pp. e2100163 - n/a
• Main Authors: Ávila‐Gálvez, María Ángeles, González‐Sarrías, Antonio, Martínez‐Díaz, Francisco, Abellán, Beatriz, Martínez‐Torrano, Alejandro José, Fernández‐López, Antonio José, Giménez‐Bastida, Juan Antonio, Espín, Juan Carlos
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 01-06-2021
• Subjects: Adult; Aged; Aged, 80 and over; Anticancer properties; Antineoplastic Agents, Phytogenic - pharmacokinetics; Antineoplastic Agents, Phytogenic - pharmacology; Antitumor activity; Apoptosis; Apoptosis - drug effects; Biopsy; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - pathology; Capsules; Cell cycle; Cell Cycle - drug effects; Cell Line, Tumor; Cell Proliferation - drug effects; clinical trial; Curcumin; Curcumin - pharmacokinetics; Curcumin - pharmacology; Diet; Dietary Supplements; Estrogen Receptor Modulators - pharmacology; Female; Humans; isoflavone; Isoflavones; lignan; Lignans; Metabolites; Metabolomics; Middle Aged; Phenols; Polyphenols; Polyphenols - metabolism; Polyphenols - pharmacokinetics; Polyphenols - pharmacology; Red clover; Resveratrol; Senescence; Surgery; Tissues; Tumors; Xenoestrogens; clinical trial; breast cancer; isoflavone; lignan; resveratrol; curcumin
• ISSN: 1613-4125; 1613-4133
• DOI: 10.1002/mnfr.202100163

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.
A total of 47 curcuminoid, isoflavone, resveratrol, and lignan‐derived metabolites, mostly conjugated, were detected in malignant mammary tissues of breast cancer patients. However, free curcumin, but not its glucuronide, was detected at micromolar concentration, likely due to a glucuronidation‐saturation process. Breast tissue‐occurring metabolites, mainly, curcuminoids, induced cell cycle arrest, senescence, and apoptosis via p53/p21, while isoflavone metabolites exerted estrogenic activity.