Articles producció científica> Ciències Mèdiques Bàsiques

Resveratrol Potently Counteracts Quercetin Starvation-Induced Autophagy and Sensitizes HepG2 Cancer Cells to Apoptosis

  • Identification data

    Identifier: imarina:3647439
    Authors:
    Tomas-Hernández S, Blanco J, Rojas C, Roca-Martínez J, Ojeda-Montes M, Beltrán-Debón R, Garcia-Vallvé S, Pujadas G, Arola L, Mulero M
    Abstract:
    Resveratrol (RSV) has been described as a potent antioxidant, anti-steatotic, and antitumor compound, and it has also been identified as a potent autophagy inducer. On the other hand, quercetin (QCT) is a dietary flavonoid with known antitumor, anti-inflammatory and antidiabetic effects. Additionally, QCT increases autophagy. To study the hypothetical synergistic effect of both compounds, we tested the combined effect of QCT and RSV on the autophagy process in HepG2 cells METHODS AND RESULTS: Autophagy was studied by western blotting, real-time RT-PCR, and cellular staining. Our results clearly indicate a bifunctional molecular effect of RSV. Both polyphenols were individually able to promote autophagy. Strikingly, when RSV was combined with QCT, it promoted a potent reduction of QCT-induced autophagy and influenced pro-apoptotic signaling. Conclusion: RSV acts differentially on the autophagic process depending on the cellular energetic state. We further characterized the molecular mechanisms related to this effect, and we observed that AMP-activated protein kinase (AMPK) phosphorylation, heme oxygenase 1 (HO-1) downregulation, lysosomal membrane permeabilization (LMP) and Zinc (Zn2+ ) dynamics could be important modulators of such RSV-related effects and could globally represent a promising strategy to sensitize cancer cells to QCT treatment. This article is protected by copyright. All rights reserved.
  • Others:

    Author, as appears in the article.: Tomas-Hernández S, Blanco J, Rojas C, Roca-Martínez J, Ojeda-Montes M, Beltrán-Debón R, Garcia-Vallvé S, Pujadas G, Arola L, Mulero M
    Department: Ciències Mèdiques Bàsiques Bioquímica i Biotecnologia
    URV's Author/s: Arola Ferrer, Luis Maria / Beltrán Debón, Raúl Alejandro / Blanco Pérez, Jordi / Garcia Vallve, Santiago / Mulero Abellán, Miguel / OJEDA MONTES, Mª JOSÉ / Pujadas Anguiano, Gerard / ROJAS DOMÍNGUEZ, CRISTINA / TOMAS HERNÁNDEZ, SARA
    Keywords: Resveratrol Quercetin Protective role Pathway P70s6 kinase Molecular-mechanisms Lysosomal membrane permeabilization Ischemia/reperfusion injury Inhibition In-vitro Human leukemia-cells Hepatic steatosis Heme oxygenase 1 Ellagic acid Death Autophagy Apoptosis Amp-activated protein kinase quercetin p70s6 kinase lysosomal membrane permeabilization heme oxygenase 1 autophagy apoptosis amp-activated protein kinase
    Abstract: Resveratrol (RSV) has been described as a potent antioxidant, anti-steatotic, and antitumor compound, and it has also been identified as a potent autophagy inducer. On the other hand, quercetin (QCT) is a dietary flavonoid with known antitumor, anti-inflammatory and antidiabetic effects. Additionally, QCT increases autophagy. To study the hypothetical synergistic effect of both compounds, we tested the combined effect of QCT and RSV on the autophagy process in HepG2 cells METHODS AND RESULTS: Autophagy was studied by western blotting, real-time RT-PCR, and cellular staining. Our results clearly indicate a bifunctional molecular effect of RSV. Both polyphenols were individually able to promote autophagy. Strikingly, when RSV was combined with QCT, it promoted a potent reduction of QCT-induced autophagy and influenced pro-apoptotic signaling. Conclusion: RSV acts differentially on the autophagic process depending on the cellular energetic state. We further characterized the molecular mechanisms related to this effect, and we observed that AMP-activated protein kinase (AMPK) phosphorylation, heme oxygenase 1 (HO-1) downregulation, lysosomal membrane permeabilization (LMP) and Zinc (Zn2+ ) dynamics could be important modulators of such RSV-related effects and could globally represent a promising strategy to sensitize cancer cells to QCT treatment. This article is protected by copyright. All rights reserved.
    Thematic Areas: Saúde coletiva Química Nutrição Medicina veterinaria Medicina ii Medicina i Interdisciplinar Food science & technology Food science Farmacia Educação física Ciências biológicas ii Ciências biológicas i Ciências agrárias i Ciência de alimentos Biotecnología Biotechnology Astronomia / física
    licence for use: https://creativecommons.org/licenses/by/3.0/es/
    ISSN: 16134125
    Author's mail: jordi.blanco@urv.cat miquel.mulero@urv.cat santi.garcia-vallve@urv.cat gerard.pujadas@urv.cat lluis.arola@urv.cat raul.beltran@urv.cat
    Author identifier: 0000-0001-8016-0984 0000-0002-0348-7497 0000-0003-2598-8089 0000-0003-2767-1974 0000-0001-9691-1906
    Record's date: 2024-09-07
    Papper version: info:eu-repo/semantics/acceptedVersion
    Link to the original source: https://onlinelibrary.wiley.com/doi/abs/10.1002/mnfr.201700610
    Licence document URL: https://repositori.urv.cat/ca/proteccio-de-dades/
    Papper original source: Molecular Nutrition & Food Research. 62 (5):
    APA: Tomas-Hernández S, Blanco J, Rojas C, Roca-Martínez J, Ojeda-Montes M, Beltrán-Debón R, Garcia-Vallvé S, Pujadas G, Arola L, Mulero M (2018). Resveratrol Potently Counteracts Quercetin Starvation-Induced Autophagy and Sensitizes HepG2 Cancer Cells to Apoptosis. Molecular Nutrition & Food Research, 62(5), -. DOI: 10.1002/mnfr.201700610
    Article's DOI: 10.1002/mnfr.201700610
    Entity: Universitat Rovira i Virgili
    Journal publication year: 2018
    Publication Type: Journal Publications
  • Keywords:

    Biotechnology,Food Science,Food Science & Technology
    Resveratrol
    Quercetin
    Protective role
    Pathway
    P70s6 kinase
    Molecular-mechanisms
    Lysosomal membrane permeabilization
    Ischemia/reperfusion injury
    Inhibition
    In-vitro
    Human leukemia-cells
    Hepatic steatosis
    Heme oxygenase 1
    Ellagic acid
    Death
    Autophagy
    Apoptosis
    Amp-activated protein kinase
    quercetin
    p70s6 kinase
    lysosomal membrane permeabilization
    heme oxygenase 1
    autophagy
    apoptosis
    amp-activated protein kinase
    Saúde coletiva
    Química
    Nutrição
    Medicina veterinaria
    Medicina ii
    Medicina i
    Interdisciplinar
    Food science & technology
    Food science
    Farmacia
    Educação física
    Ciências biológicas ii
    Ciências biológicas i
    Ciências agrárias i
    Ciência de alimentos
    Biotecnología
    Biotechnology
    Astronomia / física
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