Differential Uridyl-diphosphate-Glucuronosyl Transferase 1A enzymatic arsenal explains the specific cytotoxicity of resveratrol towards tumor colorectal cells
Resveratrol belongs to the Bioactive Food Component (BFC) family. It seems admitted that its cytotoxic action impacts tumor cells and spares healthy cells, but the published proofs remain rare. We hypothesized that cells may differentially metabolize resveratrol and lead to different systemic impact...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2022-12-01
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| Series: | Journal of Functional Foods |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1756464622004157 |
| _version_ | 1811187596955484160 |
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| author | Samuel Amintas Pauline Beaumont Charles Dupin Isabelle Moranvillier Isabelle Lamrissi Elie Patel Benjamin Fernandez Alice Bibeyran Julian Boutin Tristan Richard Stéphanie Krisa François Moreau-Gaudry Aurélie Bedel David Cappellen Benoît Pinson Véronique Vendrely Sandrine Dabernat |
| author_facet | Samuel Amintas Pauline Beaumont Charles Dupin Isabelle Moranvillier Isabelle Lamrissi Elie Patel Benjamin Fernandez Alice Bibeyran Julian Boutin Tristan Richard Stéphanie Krisa François Moreau-Gaudry Aurélie Bedel David Cappellen Benoît Pinson Véronique Vendrely Sandrine Dabernat |
| author_sort | Samuel Amintas |
| collection | DOAJ |
| description | Resveratrol belongs to the Bioactive Food Component (BFC) family. It seems admitted that its cytotoxic action impacts tumor cells and spares healthy cells, but the published proofs remain rare. We hypothesized that cells may differentially metabolize resveratrol and lead to different systemic impacts. For this, resveratrol metabolization was evaluated by ultra-high-performance liquid chromatography (UHPLC) coupled with diode array detection (DAD), and correlated with the expression of Uridyl-diphosphate-Glucuronosyl Transferase 1A (UGT1A) genes. The expression of UGT1A genes in human colorectal tissues was studied with RNAseq databases. Functional validation of UGT1A enzymes implication in resveratrol sensitivity of colorectal cells established by UGT1A expression modulation. As resveratrol impacts the S phase of the cell cycle, nucleotide metabolic balance was assessed. We found that resveratrol was more cytotoxic in cells with downregulation of UGTs, i.e. tumor cells. Conversely, overexpression of the UGT1A10 gene in an initial resveratrol-sensitive tumor cell line restored the metabolization accompanied by cytotoxicity diminution. Resveratrol affected intestinal sensitive tumor cell homeostasis with a cell growth/proliferation decoupling, cell-cycle modulation, and UXP/AXP nucleotide imbalance resulting in a global reduction of transcription and translation. This impact on global cell activity was restricted to tumor cells. This study improves resveratrol’s general knowledge and explains how its antitumor action can spare non-tumor cells. It also paves the way to select colorectal tumors eligible for resveratrol treatment potentiation without additional toxicity to healthy digestive tissues. |
| first_indexed | 2024-04-11T14:06:07Z |
| format | Article |
| id | doaj.art-a6b60731bfbd48399c87283fc03376bc |
| institution | Directory Open Access Journal |
| issn | 1756-4646 |
| language | English |
| last_indexed | 2024-04-11T14:06:07Z |
| publishDate | 2022-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Functional Foods |
| spelling | doaj.art-a6b60731bfbd48399c87283fc03376bc2022-12-22T04:19:53ZengElsevierJournal of Functional Foods1756-46462022-12-0199105345Differential Uridyl-diphosphate-Glucuronosyl Transferase 1A enzymatic arsenal explains the specific cytotoxicity of resveratrol towards tumor colorectal cellsSamuel Amintas0Pauline Beaumont1Charles Dupin2Isabelle Moranvillier3Isabelle Lamrissi4Elie Patel5Benjamin Fernandez6Alice Bibeyran7Julian Boutin8Tristan Richard9Stéphanie Krisa10François Moreau-Gaudry11Aurélie Bedel12David Cappellen13Benoît Pinson14Véronique Vendrely15Sandrine Dabernat16BoRdeaux institute In onCology – BRIC U1312, INSERM, Univ. Bordeaux, CHU de Bordeaux, Service de biologie des tumeurs et Tumorothèque, Bordeaux, FranceUR Oenologie, EA 4577, USC 1366 INRAE, INP, ISVV, Univ. Bordeaux, Villenave d'Ornon, FranceBoRdeaux institute In onCology – BRIC U1312, INSERM, Univ. Bordeaux, CHU de Bordeaux, Service de Radiothérapie, Bordeaux, FranceBoRdeaux institute In onCology – BRIC U1312, INSERM, Univ. Bordeaux, Bordeaux, FranceBoRdeaux institute In onCology – BRIC U1312, INSERM, Univ. Bordeaux, Bordeaux, FranceBoRdeaux institute In onCology – BRIC U1312, INSERM, Univ. Bordeaux, Bordeaux, FranceBoRdeaux institute In onCology – BRIC U1312, INSERM, Univ. Bordeaux, CHU de Bordeaux, Service de chirurgie digestive, Bordeaux, FrancePlateforme Vect’UB, TBMcore - Univ. Bordeaux, Bordeaux, FranceBoRdeaux institute In onCology – BRIC U1312, INSERM, Univ. Bordeaux, CHU de Bordeaux, Service de Biochimie et Biologie moléculaire, Bordeaux, FranceUR Oenologie, EA 4577, USC 1366 INRAE, INP, ISVV, Univ. Bordeaux, Villenave d'Ornon, FranceUR Oenologie, EA 4577, USC 1366 INRAE, INP, ISVV, Univ. Bordeaux, Villenave d'Ornon, FranceBoRdeaux institute In onCology – BRIC U1312, INSERM, Univ. Bordeaux, CHU de Bordeaux, Service de Biochimie et Biologie moléculaire, Bordeaux, FranceBoRdeaux institute In onCology – BRIC U1312, INSERM, Univ. Bordeaux, CHU de Bordeaux, Service de Biochimie et Biologie moléculaire, Bordeaux, FranceBoRdeaux institute In onCology – BRIC U1312, INSERM, Univ. Bordeaux, CHU de Bordeaux, Service de biologie des tumeurs et Tumorothèque, Bordeaux, FranceUMR 5095, CNRS, Institut de Biochimie et Génétique Cellulaires, 33077 Bordeaux, France; Service Analyses Métabolique, TBMcore - Univ. Bordeaux - CNRS UAR 3427 - INSERM US005, FranceBoRdeaux institute In onCology – BRIC U1312, INSERM, Univ. Bordeaux, CHU de Bordeaux, Service de Radiothérapie, Bordeaux, FranceBoRdeaux institute In onCology – BRIC U1312, INSERM, Univ. Bordeaux, CHU de Bordeaux, Service de Biochimie et Biologie moléculaire, Bordeaux, France; Corresponding author at: Université de Bordeaux, INSERM U1312, Bordeaux Institute of Oncology (BRIC), 146, Rue Léo Saignat, 33076 Bordeaux Cedex, France.Resveratrol belongs to the Bioactive Food Component (BFC) family. It seems admitted that its cytotoxic action impacts tumor cells and spares healthy cells, but the published proofs remain rare. We hypothesized that cells may differentially metabolize resveratrol and lead to different systemic impacts. For this, resveratrol metabolization was evaluated by ultra-high-performance liquid chromatography (UHPLC) coupled with diode array detection (DAD), and correlated with the expression of Uridyl-diphosphate-Glucuronosyl Transferase 1A (UGT1A) genes. The expression of UGT1A genes in human colorectal tissues was studied with RNAseq databases. Functional validation of UGT1A enzymes implication in resveratrol sensitivity of colorectal cells established by UGT1A expression modulation. As resveratrol impacts the S phase of the cell cycle, nucleotide metabolic balance was assessed. We found that resveratrol was more cytotoxic in cells with downregulation of UGTs, i.e. tumor cells. Conversely, overexpression of the UGT1A10 gene in an initial resveratrol-sensitive tumor cell line restored the metabolization accompanied by cytotoxicity diminution. Resveratrol affected intestinal sensitive tumor cell homeostasis with a cell growth/proliferation decoupling, cell-cycle modulation, and UXP/AXP nucleotide imbalance resulting in a global reduction of transcription and translation. This impact on global cell activity was restricted to tumor cells. This study improves resveratrol’s general knowledge and explains how its antitumor action can spare non-tumor cells. It also paves the way to select colorectal tumors eligible for resveratrol treatment potentiation without additional toxicity to healthy digestive tissues.http://www.sciencedirect.com/science/article/pii/S1756464622004157Bioactive food componentsUGTDrug sensitivityColorectal cancerTumorigenesisNucleotide metabolism |
| spellingShingle | Samuel Amintas Pauline Beaumont Charles Dupin Isabelle Moranvillier Isabelle Lamrissi Elie Patel Benjamin Fernandez Alice Bibeyran Julian Boutin Tristan Richard Stéphanie Krisa François Moreau-Gaudry Aurélie Bedel David Cappellen Benoît Pinson Véronique Vendrely Sandrine Dabernat Differential Uridyl-diphosphate-Glucuronosyl Transferase 1A enzymatic arsenal explains the specific cytotoxicity of resveratrol towards tumor colorectal cells Journal of Functional Foods Bioactive food components UGT Drug sensitivity Colorectal cancer Tumorigenesis Nucleotide metabolism |
| title | Differential Uridyl-diphosphate-Glucuronosyl Transferase 1A enzymatic arsenal explains the specific cytotoxicity of resveratrol towards tumor colorectal cells |
| title_full | Differential Uridyl-diphosphate-Glucuronosyl Transferase 1A enzymatic arsenal explains the specific cytotoxicity of resveratrol towards tumor colorectal cells |
| title_fullStr | Differential Uridyl-diphosphate-Glucuronosyl Transferase 1A enzymatic arsenal explains the specific cytotoxicity of resveratrol towards tumor colorectal cells |
| title_full_unstemmed | Differential Uridyl-diphosphate-Glucuronosyl Transferase 1A enzymatic arsenal explains the specific cytotoxicity of resveratrol towards tumor colorectal cells |
| title_short | Differential Uridyl-diphosphate-Glucuronosyl Transferase 1A enzymatic arsenal explains the specific cytotoxicity of resveratrol towards tumor colorectal cells |
| title_sort | differential uridyl diphosphate glucuronosyl transferase 1a enzymatic arsenal explains the specific cytotoxicity of resveratrol towards tumor colorectal cells |
| topic | Bioactive food components UGT Drug sensitivity Colorectal cancer Tumorigenesis Nucleotide metabolism |
| url | http://www.sciencedirect.com/science/article/pii/S1756464622004157 |
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