Laboratory of Food & Health, Research Group on Quality, Safety and Bioactivity of Plant Foods, CEBAS-CSIC, Campus de Espinardo, 30100, Murcia, Spain.
Reina Sofía University Hospital, Service of Anatomical Pathology, Avda. Intendente Jorge Palacios s/n, 30003, Murcia, Spain.
Mol Nutr Food Res. 2019 May;63(9):e1801239. doi: 10.1002/mnfr.201801239. Epub 2019 Feb 4.
Dietary polyphenols may protect against breast cancer. However, it is unknown whether polyphenols reach human malignant breast tumors in molecular forms and(or) at concentrations likely to act against cancer.
Ninteen breast cancer patients consumed three capsules daily from biopsy-confirmed diagnosis to surgery (6 ± 2 days). The capsules contained pomegranate, orange, lemon, olive, cocoa, and grapeseed extracts plus resveratrol, providing 37 different phenolics (473.7 mg), theobromine and caffeine (19.7 mg). A total of 101 metabolites are identified in urine, 69 in plasma, 39 in normal (NT), and 33 in malignant (MT) tissues by UPLC-ESI-QTOF-MS. Eight control patients did not consume extracts. Phenolic-derived metabolites in MT and NT are mainly glucuronidated and(or) sulfated. Some representative metabolites detected in MT (median and range, pmol g ) are urolithin-A-3-O-glucuronide (26.2; 3.2-66.5), 2,5-dihydroxybenzoic acid (40.2; 27.7-52.2), resveratrol-3-O-sulfate (86.4; 7.8-224.4), dihydroresveratrol-3-O-glucuronide (109.9; 10.3-229.4), and theobromine (715.0; 153.9-3,216). Metabolites, as detected in breast tissues, do not exert antiproliferative or estrogenic/antiestrogenic activities in MCF-7 breast cancer cells.
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.
膳食多酚可能有助于预防乳腺癌。然而，尚不清楚多酚是否以可能抗癌的分子形式和（或）浓度到达人类恶性乳腺肿瘤。
19 名乳腺癌患者从活检确诊到手术（6±2 天）期间每天服用三粒胶囊。胶囊中含有石榴、橙子、柠檬、橄榄、可可和葡萄籽提取物以及白藜芦醇，提供了 37 种不同的酚类化合物（473.7mg）、可可碱和咖啡因（19.7mg）。通过 UPLC-ESI-QTOF-MS 在尿液中鉴定出 101 种代谢物，在血浆中鉴定出 69 种代谢物，在正常（NT）组织中鉴定出 39 种代谢物，在恶性（MT）组织中鉴定出 33 种代谢物。8 名对照患者未服用提取物。MT 和 NT 中酚类衍生代谢物主要为葡萄糖醛酸化和（或）硫酸化。在 MT 中检测到的一些代表性代谢物（中位数和范围，pmol/g）为乌洛托品-A-3-O-葡萄糖苷（26.2；3.2-66.5）、2,5-二羟基苯甲酸（40.2；27.7-52.2）、白藜芦醇-3-O-硫酸盐（86.4；7.8-224.4）、二氢白藜芦醇-3-O-葡萄糖苷（109.9；10.3-229.4）和可可碱（715.0；153.9-3,216）。在 MCF-7 乳腺癌细胞中，如在乳腺组织中检测到的代谢物，没有发挥抗增殖或雌激素/抗雌激素活性。
这是第一项全面描述膳食酚类化合物和黄嘌呤在 MT 和 NT 中代谢特征的研究。虽然二期共轭可能会阻碍直接的抗癌活性，但长期的肿瘤衰老化学预防也不能被排除。
