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      Flavonoids as Anticancer Agents

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          Abstract

          Flavonoids are polyphenolic compounds subdivided into 6 groups: isoflavonoids, flavanones, flavanols, flavonols, flavones and anthocyanidins found in a variety of plants. Fruits, vegetables, plant-derived beverages such as green tea, wine and cocoa-based products are the main dietary sources of flavonoids. Flavonoids have been shown to possess a wide variety of anticancer effects: they modulate reactive oxygen species (ROS)-scavenging enzyme activities, participate in arresting the cell cycle, induce apoptosis, autophagy, and suppress cancer cell proliferation and invasiveness. Flavonoids have dual action regarding ROS homeostasis—they act as antioxidants under normal conditions and are potent pro-oxidants in cancer cells triggering the apoptotic pathways and downregulating pro-inflammatory signaling pathways. This article reviews the biochemical properties and bioavailability of flavonoids, their anticancer activity and its mechanisms of action.

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          Benefits of polyphenols on gut microbiota and implications in human health.

          Fernando Cardona, Cristina Andres-Lacueva, Sara Tulipani … (2013)
          The biological properties of dietary polyphenols are greatly dependent on their bioavailability that, in turn, is largely influenced by their degree of polymerization. The gut microbiota play a key role in modulating the production, bioavailability and, thus, the biological activities of phenolic metabolites, particularly after the intake of food containing high-molecular-weight polyphenols. In addition, evidence is emerging on the activity of dietary polyphenols on the modulation of the colonic microbial population composition or activity. However, although the great range of health-promoting activities of dietary polyphenols has been widely investigated, their effect on the modulation of the gut ecology and the two-way relationship "polyphenols ↔ microbiota" are still poorly understood. Only a few studies have examined the impact of dietary polyphenols on the human gut microbiota, and most were focused on single polyphenol molecules and selected bacterial populations. This review focuses on the reciprocal interactions between the gut microbiota and polyphenols, the mechanisms of action and the consequences of these interactions on human health. Copyright © 2013 Elsevier Inc. All rights reserved.
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            Interactions of polyphenols with carbohydrates, lipids and proteins.

            Lidija Jakobek (2015)
            Polyphenols are secondary metabolites in plants, investigated intensively because of their potential positive effects on human health. Their bioavailability and mechanism of positive effects have been studied, in vitro and in vivo. Lately, a high number of studies takes into account the interactions of polyphenols with compounds present in foods, like carbohydrates, proteins or lipids, because these food constituents can have significant effects on the activity of phenolic compounds. This paper reviews the interactions between phenolic compounds and lipids, carbohydrates and proteins and their impact on polyphenol activity.
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              Tumour hypoxia induces a metabolic shift causing acidosis: a common feature in cancer

              Johanna Chiche, M Brahimi-Horn, Jacques Pouysségur (2009)
              Abstract Maintenance of cellular pH homeostasis is fundamental to life. A number of key intracellular pH (pHi) regulating systems including the Na+/H+ exchangers, the proton pump, the monocarboxylate transporters, the HCO3 − transporters and exchangers and the membrane-associated and cytosolic carbonic anhydrases cooperate in maintaining a pHi that is permissive for cell survival. A common feature of tumours is acidosis caused by hypoxia (low oxygen tension). In addition to oncogene activation and transformation, hypoxia is responsible for inducing acidosis through a shift in cellular metabolism that generates a high acid load in the tumour microenvironment. However, hypoxia and oncogene activation also allow cells to adapt to the potentially toxic effects of an excess in acidosis. Hypoxia does so by inducing the activity of a transcription factor the hypoxia-inducible factor (HIF), and particularly HIF-1, that in turn enhances the expression of a number of pHi-regulating systems that cope with acidosis. In this review, we will focus on the characterization and function of some of the hypoxia-inducible pH-regulating systems and their induction by hypoxic stress. It is essential to understand the fundamentals of pH regulation to meet the challenge consisting in targeting tumour metabolism and acidosis as an anti-tumour approach. We will summarize strategies that take advantage of intracellular and extracellular pH regulation to target the primary tumour and metastatic growth, and to turn around resistance to chemotherapy and radiotherapy.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Nutrients
                Journal ID (iso-abbrev): Nutrients
                Journal ID (publisher-id): nutrients
                Title: Nutrients
                Publisher: MDPI
                ISSN (Electronic): 2072-6643
                Publication date (Electronic): 12 February 2020
                Publication date Collection: February 2020
                Volume: 12
                Issue: 2
                Electronic Location Identifier: 457
                Affiliations
                [1 ]Institute of Pharmaceutical Technologies, Faculty of Pharmacy, Medical Academy, Lithuanian University of Health Sciences, LT-50161 Kaunas, Lithuania; DaliaMarija.Kopustinskiene@ 123456lsmuni.lt (D.M.K.); Valdas.Jakstas@ 123456lsmuni.lt (V.J.)
                [2 ]Department of Pharmacognosy, Medical Academy, Lithuanian University of Health Sciences, LT-50161 Kaunas, Lithuania
                [3 ]Department of Drug Technology and Social Pharmacy, Faculty of Pharmacy, Medical Academy, Lithuanian University of Health Sciences, Sukileliu pr. 13, LT-50161 Kaunas, Lithuania; Arunas.Savickas@ 123456lsmuni.lt
                Author notes
                Author information
                https://orcid.org/0000-0002-3399-2849
                https://orcid.org/0000-0001-7627-6263
                https://orcid.org/0000-0003-1744-2932
                Article
                Publisher ID: nutrients-12-00457
                DOI: 10.3390/nu12020457
                PMC ID: 7071196
                PubMed ID: 32059369
                SO-VID: 4ff047c7-fe4c-4fd2-869c-36dd4b7bc44d
                Copyright © © 2020 by the authors.
                License:

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                Date received : 29 January 2020
                Date accepted : 10 February 2020
                Categories
                Subject: Review

                ScienceOpen disciplines: Nutrition & Dietetics
                Keywords: flavonoids,cancer,ros,antioxidants,pro-oxidants,mitochondria
                Data availability:
                ScienceOpen disciplines: Nutrition & Dietetics
                Keywords: flavonoids, cancer, ros, antioxidants, pro-oxidants, mitochondria

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