An Update on the Effects of Glyceollins on Human Health Possible Anticancer Effects and Underlying Mechanisms Thu Ha Pham, Sylvain Lecomte, Theo Efstathiou, François Ferriere, Farzad Pakdel To cite this version: Thu Ha Pham, Sylvain Lecomte, Theo Efstathiou, François Ferriere, Farzad Pakdel. An Update on the Effects of Glyceollins on Human Health Possible Anticancer Effects and Underlying Mechanisms. Nutrients, MDPI, 2019, 11 (1), pp.79. 10.3390/nu11010079. hal-01978725 HAL Id: hal-01978725 https://hal-univ-rennes1.archives-ouvertes.fr/hal-01978725 Submitted on 8 Jul 2020 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. nutrients Review An Update on the Effects of Glyceollins on Human Health: Possible Anticancer Effects and Underlying Mechanisms Thu Ha Pham 1, Sylvain Lecomte 1, Theo Efstathiou 2, Francois Ferriere 1 and Farzad Pakdel 1,* 1 Univ Rennes, Inserm, EHESP, Irset (Institut de recherche en santé, environnement et travail)—UMR_S 1085, F-35000 Rennes, France; [email protected] (T.H.P.); [email protected] (S.L.); [email protected] (F.F.) 2 Laboratoire Nutrinov, Technopole Atalante Champeaux, 8 rue Jules Maillard de la Gournerie, 35012 Rennes Cedex, France; [email protected] * Correspondence: [email protected]; Tel.: +33-(0)22-323-5132 Received: 29 November 2018; Accepted: 23 December 2018; Published: 3 January 2019 Abstract: Biologically active plant-based compounds, commonly referred to as phytochemicals, can influence the expression and function of various receptors and transcription factors or signaling pathways that play vital roles in cellular functions and are then involved in human health and diseases. Thus, phytochemicals may have a great potential to prevent and treat chronic diseases. Glyceollins, a group of phytoalexins that are isolated from soybeans, have attracted attention because they exert numerous effects on human functions and diseases, notably anticancer effects. In this review, we have presented an update on the effects of glyceollins in relation to their potential beneficial roles in human health. Despite a growing number of studies suggesting that this new family of phytochemicals can be involved in critical cellular pathways, such as estrogen receptor, protein kinase, and lipid kinase signaling pathways, future investigations will be needed to better understand their molecular mechanisms and their specific significance in biomedical applications. Keywords: glyceollins; phytochemicals; dietary compounds; signaling pathways; estrogen receptor; breast cancer; human health 1. Introduction Thousands of bioactive molecules, among phytochemicals, naturally occur in plants after secondary metabolism. Out of these compounds, polyphenols represent the most important family, including more than 500 identified compounds [1,2]. They are mainly composed of flavonoids, phenolic acids, stilbenes, and lignans, found in a wide variety of plant-based foods. Polyphenol concentrations in foods and quantities consumed differ considerably, leading to wide differences in the daily intake between polyphenol compounds [2]. Polyphenols have often been associated with a decreased incidence of several human diseases and have been used in traditional medicines and functional foods [3]. Epidemiological studies have shown that a high intake of polyphenolic phytochemicals in the diet can prevent many diseases, such as cancers, diabetes or inflammatory, cardiovascular, and neurodegenerative diseases [4–9]. However, these studies have some limitations because they do not always take into account the geographical diversity, sex, age, and region of residence of the subjects. In addition, an accurate evaluation of polyphenol intake, which appears to be essential in these studies, is not always completed [2,8]. Polyphenols are also used as food supplements and in pharmaceutical and cosmetic products [10–12]. One of the advantages of ingesting phytochemicals through the diet is that combinatory effects from these compounds can occur [9]. Nutrients 2019, 11, 79; doi:10.3390/nu11010079 www.mdpi.com/journal/nutrients NutrientsNutrients2019 2018, 11, 10, 79, x FOR PEER REVIEW 22 ofof 24 24 The phytoalexins, a group of polyphenolic compounds possessing strong antimicrobial and antifungalThe phytoalexins, properties, aare group produced of polyphenolic by plants as compounds defense molecules possessing against strong phytopathogens antimicrobial and[13]. antifungalThey are only properties, present are in very produced small byquantities plants asin defensehealthy plants, molecules but againstaccumulate phytopathogens in large quantities [13]. Theyfollowing are only an presentattack by in verybacteria, small fungi, quantities or nemato in healthydes [14,15]. plants, butIn addition accumulate to biotic in large agents, quantities other followingstresses, ansuch attack as high by bacteria,temperature, fungi, ultraviolet or nematodes (UV) [ 14radiation,,15]. In addition humidity, to and biotic dryness, agents, can other also stresses, induce suchthe production as high temperature, of these compounds ultraviolet [14,15]. (UV) radiation, Phytoalexins humidity, are very and diverse dryness, and can have also been induce found the in productionvarious crops, of these such compounds as rice [16], [14 soybean,15]. Phytoalexins [17], maize are [18], very barley diverse [19], and and have banana been [20]. found Phytoalexins in various crops,can be such produced as rice in [16 numerous], soybean parts [17], of maize the plant, [18], su barleych as [the19], flowers, and banana leaves, [20 stems,]. Phytoalexins seeds, and canroot betubers produced [19,21]. in numerous parts of the plant, such as the flowers, leaves, stems, seeds, and root tubersGlyceollins, [19,21]. a group of phytoalexins, are the most important bioactive compounds present in soybeansGlyceollins, upon exposure a group ofto phytoalexins,certain fungi and are thesome most abiotic important elicitors, bioactive such as compoundsUV light, aluminum present inchloride, soybeans or upon methyl exposure jasmonate to certain [17,22]. fungi Glyceollin and some I, abioticII, and elicitors, III (GI, suchGII, asand UV GIII) light, are aluminum de novo chloride,synthesized or methyl from jasmonatethe soy isoflavone [17,22]. Glyceollin daidzein. I, II,In and addition III (GI, to GII, their and GIII)antibacterial, are de novo antifungal, synthesized and fromantinematode the soy isoflavone actions, daidzein.glyceollins In additionhave recently to their received antibacterial, much antifungal, attention andbecause antinematode of their actions,antiproliferative, glyceollins antiestrogenic, have recently anti-inflammatory, received much antioxidative, attention because and anticholesterolemic of their antiproliferative, activities. antiestrogenic,They may possess anti-inflammatory, potential medicinal antioxidative, properties and anticholesterolemic in humans, notably activities. protective They effects may possess against potentialhormone-dependent medicinal properties cancers, and in humans, metabolic notably and cardia protectivec diseases effects (Figure against 1) hormone-dependent [23,24]. Accordingly, cancers,glyceollins and metabolicare effectively and cardiac able diseases to inhibit (Figure proinflammatory1)[ 23,24]. Accordingly, cytokines glyceollins by areinhibiting effectively the ableactivation/phosphorylation to inhibit proinflammatory of the cytokines transcription by inhibitingnuclear factor-kappa the activation/phosphorylation B (NF-κB). They prevented of the the transcriptionlipopolysaccharide nuclear (LPS)-induced factor-kappa B expression (NF-κB). They of ni preventedtric oxide thesynthase lipopolysaccharide (iNOS) and cyclo-oxygenase (LPS)-induced expression(COX)-2 in of murine nitric oxide macrophage synthase cell (iNOS) lines and and cyclo-oxygenase were able to reduce (COX)-2 12- inO-tetradecanoylphorbol-13- murine macrophage cell linesacetate and (TPA)-induced were able to reduce skin 12-inflammationO-tetradecanoylphorbol-13-acetate in mice. These natural (TPA)-inducedcompounds also skin inhibit inflammation hormone- independent mice. These breast natural and compoundsovarian cancer also cell inhibit growth hormone-dependent [25,26]. One of the mechanisms breast and ovarian responsible cancer for cell the growthantitumoral [25,26 ].effect One ofof the glyceollins mechanisms is responsibletheir antiestrogenic for the antitumoral action [25,27,28]. effect of glyceollins However, is theirother antiestrogenicantitumorigenic action actions, [25,27 whose,28]. However, mechanisms other are antitumorigenic not well understood, actions, of whose glyceollins mechanisms have also are been not wellreported. understood, For instance, of glyceollins Lee et al. have repo alsorted on been an reported.inhibitory Foreffect instance, of glyceollins Lee et on al. the reported kinase activity on an inhibitoryof the vascular effect of endothelial glyceollins ongrowth the kinase factor activity (VEG ofF) thereceptor vascular as endothelial well as its growth