Potential antiproliferative activity of polyphenol metabolites against human breast cancer cells and their urine excretion pattern in healthy subjects following acute intake of a polyphenol-rich juice of grumixama (Eugenia brasiliensis Lam.)

Abstract

The bioavailability and metabolism of anthocyanins and ellagitannins following acute intake of grumixama fruit, native Brazilian cherry, by humans, and its in vitro antiproliferative activity against breast cancer cells (MDA-MB-231) were investigated. A single dose of grumixama juice was administered to healthy women (n = 10) and polyphenol metabolites were analyzed in urine and plasma samples collected over 24 h. The majority of the metabolites circulating and excreted in urine were phenolic acids and urolithin conjugates, the gut microbiota catabolites of both classes of polyphenols, respectively. According to pharmacokinetic parameters, the subjects were divided into two distinct groups, high and low urinary metabolite excretors. The pool of polyphenol metabolites found in urine samples showed a significant inhibition of cell proliferation and G2/M cell cycle arrest in MDA-MB-231 cells. Our findings demonstrate the large interindividual variability concerning the polyphenol metabolism, which possibly could reflect in health promotion.

The Role of the Gut Microbiota in the Metabolism of Polyphenols as Characterized by Gnotobiotic Mice

“…These processes are known to influence psychological and cognitive resilience in, for example, animal models of social defeat and sleep deprivation. The collective evidence from our group and from other investigators [83, 122–129] implicates gut-derived biologically available phenolic metabolites as primary facilitators of the observed health benefits associated with polyphenol rich diets.…”

The Two-Way Polyphenols-Microbiota Interactions and Their Effects on Obesity and Related Metabolic Diseases

“…However, some subjects excrete high amounts of polyphenol metabolites in the urine, whereas others excrete low amounts of metabolite. These findings indicate the high interindividual variability regarding polyphenol metabolism (45). Another recent study (43) showed that pomegranate ellagitannins differently improved CVD biomarkers depending on the individual's urolithin metabotypes (UM).…”

Food Ellagitannins: Structure, Metabolomic Fate, and Biological Properties

“…Pedunculagin, strictinin, castalagin, vescalagin [12] 16 [12] Chestnuts (Castanea sativa) Castalagin [7] 149 [13] Pecans (Carya illinoinensis) Pedunculagin [7] 316 [13] Walnuts (Juglans regia) Pedunculagin, casuarictin [14] 864 [13] local importance have been identified such as jabuticaba [4], guava, [5] and grumixama cherries [12]. It is interesting to note that according to a Brazilian research team, Jabuticaba berries from a particular variety cultivated in south Brazil have the highest registered ET content in fruits.…”

“…This inhibition was attributed to a significant G2/M cell cycle arrest (apoptosis) occurred in MDA-MB-231 cells, and was demonstrated by the increase in sub-G0/ G1 populations. Additionally, the authors linked this inhibition to a possible synergy among anthocyanins and urolithins [12]. Then, the modulation of the positiveestrogen receptor in breast cancer cells (MCF7) is probably one of the potential actions of urolithin conjugates.…”