Nanomolar resveratrol reduces early alterations of pancreatitis and pancreatic cancer in pancreatic acinar cells
Resveratrol is a natural phytoalexin present in human diet with a potential beneficial effect in many diseases including chronic and acute pancreatitis, a potentially fatal disease with significant morbimortality accompanied with obscure pathogenesis and without effective treatments. Resveratrol has...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-08-01
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| Series: | Phytomedicine Plus |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2667031322000847 |
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| author | Thiago M.C. Pereira Glaucimeire R. Carvalho María Luaces-Regueira Ana Bugallo-Casal Ana Iglesias-Mejuto Lonneke Nugteren Martina Schmidt Dolores Viña Elisardo C. Vasquez Manuel Campos-Toimil |
| author_facet | Thiago M.C. Pereira Glaucimeire R. Carvalho María Luaces-Regueira Ana Bugallo-Casal Ana Iglesias-Mejuto Lonneke Nugteren Martina Schmidt Dolores Viña Elisardo C. Vasquez Manuel Campos-Toimil |
| author_sort | Thiago M.C. Pereira |
| collection | DOAJ |
| description | Resveratrol is a natural phytoalexin present in human diet with a potential beneficial effect in many diseases including chronic and acute pancreatitis, a potentially fatal disease with significant morbimortality accompanied with obscure pathogenesis and without effective treatments. Resveratrol has also been shown to be a promising anti-tumor molecule on the millimolar scale. In this study, the protective effects of nanomolar concentrations of resveratrol against early events common to pancreatic cancer and pancreatitis induced by supra-physiological concentrations of cholecystokinin (CCK, 100 nM) were evaluated. Resveratrol (200, 500 nM) reduced CCK-induced intracellular trypsin activation and cell injury in isolated rat pancreatic acinar cells (PAC). The damage induced by high CCK and the protective effect of resveratrol was also measured in pancreatic tissue explants by analyzing histological changes. Finally, the effect of resveratrol on the CCK-enhanced nuclear factor κB (NF-κB) expression was studied by Western blot experiments in the AR42J pancreatic acinar cell line. Our results show, for the first time, the ability of resveratrol to reduce premature intracellular activation of trypsin and necrosis in PAC. It is suggested that resveratrol counteracts CCK-induced pancreatic tissue breakdown by downregulation of NF-κB in the nuclear fraction. Since these effects occur at nanomolar concentrations that can be achieved by oral intake, our results suggest that dietary consumption of resveratrol could have a preventive effect and delay the evolution of pancreatitis and pancreatic cancer. |
| first_indexed | 2024-12-12T14:03:12Z |
| format | Article |
| id | doaj.art-7e19d4eb16b94265aba7caed41481e23 |
| institution | Directory Open Access Journal |
| issn | 2667-0313 |
| language | English |
| last_indexed | 2024-12-12T14:03:12Z |
| publishDate | 2022-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Phytomedicine Plus |
| spelling | doaj.art-7e19d4eb16b94265aba7caed41481e232022-12-22T00:22:17ZengElsevierPhytomedicine Plus2667-03132022-08-0123100301Nanomolar resveratrol reduces early alterations of pancreatitis and pancreatic cancer in pancreatic acinar cellsThiago M.C. Pereira0Glaucimeire R. Carvalho1María Luaces-Regueira2Ana Bugallo-Casal3Ana Iglesias-Mejuto4Lonneke Nugteren5Martina Schmidt6Dolores Viña7Elisardo C. Vasquez8Manuel Campos-Toimil9Physiology and Pharmacology of Chronic Diseases (FIFAEC), Center for Research in Molecular Medicine and Chronic Diseases (CiMUS), University of Santiago de Compostela 15782, Spain; Pharmaceutical Sciences Graduate Program, Vila Velha University, Vila Velha, ES, Brazil; Federal Institute of Education, Science and Technology (IFES), Vila Velha, ES, BrazilPharmaceutical Sciences Graduate Program, Vila Velha University, Vila Velha, ES, BrazilPhysiology and Pharmacology of Chronic Diseases (FIFAEC), Center for Research in Molecular Medicine and Chronic Diseases (CiMUS), University of Santiago de Compostela 15782, SpainPhysiology and Pharmacology of Chronic Diseases (FIFAEC), Center for Research in Molecular Medicine and Chronic Diseases (CiMUS), University of Santiago de Compostela 15782, Spain; Clinical Neuroscience Research Laboratory, Health Research Institute of Santiago de Compostela (IDIS), Santiago de Compostela, SpainPhysiology and Pharmacology of Chronic Diseases (FIFAEC), Center for Research in Molecular Medicine and Chronic Diseases (CiMUS), University of Santiago de Compostela 15782, SpainPhysiology and Pharmacology of Chronic Diseases (FIFAEC), Center for Research in Molecular Medicine and Chronic Diseases (CiMUS), University of Santiago de Compostela 15782, Spain; Department of Molecular Pharmacology, University of Groningen, Groningen, the NetherlandsDepartment of Molecular Pharmacology, University of Groningen, Groningen, the NetherlandsPhysiology and Pharmacology of Chronic Diseases (FIFAEC), Center for Research in Molecular Medicine and Chronic Diseases (CiMUS), University of Santiago de Compostela 15782, SpainPharmaceutical Sciences Graduate Program, Vila Velha University, Vila Velha, ES, BrazilPhysiology and Pharmacology of Chronic Diseases (FIFAEC), Center for Research in Molecular Medicine and Chronic Diseases (CiMUS), University of Santiago de Compostela 15782, Spain; Corresponding author.Resveratrol is a natural phytoalexin present in human diet with a potential beneficial effect in many diseases including chronic and acute pancreatitis, a potentially fatal disease with significant morbimortality accompanied with obscure pathogenesis and without effective treatments. Resveratrol has also been shown to be a promising anti-tumor molecule on the millimolar scale. In this study, the protective effects of nanomolar concentrations of resveratrol against early events common to pancreatic cancer and pancreatitis induced by supra-physiological concentrations of cholecystokinin (CCK, 100 nM) were evaluated. Resveratrol (200, 500 nM) reduced CCK-induced intracellular trypsin activation and cell injury in isolated rat pancreatic acinar cells (PAC). The damage induced by high CCK and the protective effect of resveratrol was also measured in pancreatic tissue explants by analyzing histological changes. Finally, the effect of resveratrol on the CCK-enhanced nuclear factor κB (NF-κB) expression was studied by Western blot experiments in the AR42J pancreatic acinar cell line. Our results show, for the first time, the ability of resveratrol to reduce premature intracellular activation of trypsin and necrosis in PAC. It is suggested that resveratrol counteracts CCK-induced pancreatic tissue breakdown by downregulation of NF-κB in the nuclear fraction. Since these effects occur at nanomolar concentrations that can be achieved by oral intake, our results suggest that dietary consumption of resveratrol could have a preventive effect and delay the evolution of pancreatitis and pancreatic cancer.http://www.sciencedirect.com/science/article/pii/S2667031322000847Pancreatic acinar cells,Pancreatic cancer,Pancreatitis,ResveratrolCCK: cholecystokininDMEM: Dulbecco´s modified eagle medium |
| spellingShingle | Thiago M.C. Pereira Glaucimeire R. Carvalho María Luaces-Regueira Ana Bugallo-Casal Ana Iglesias-Mejuto Lonneke Nugteren Martina Schmidt Dolores Viña Elisardo C. Vasquez Manuel Campos-Toimil Nanomolar resveratrol reduces early alterations of pancreatitis and pancreatic cancer in pancreatic acinar cells Phytomedicine Plus Pancreatic acinar cells, Pancreatic cancer, Pancreatitis, Resveratrol CCK: cholecystokinin DMEM: Dulbecco´s modified eagle medium |
| title | Nanomolar resveratrol reduces early alterations of pancreatitis and pancreatic cancer in pancreatic acinar cells |
| title_full | Nanomolar resveratrol reduces early alterations of pancreatitis and pancreatic cancer in pancreatic acinar cells |
| title_fullStr | Nanomolar resveratrol reduces early alterations of pancreatitis and pancreatic cancer in pancreatic acinar cells |
| title_full_unstemmed | Nanomolar resveratrol reduces early alterations of pancreatitis and pancreatic cancer in pancreatic acinar cells |
| title_short | Nanomolar resveratrol reduces early alterations of pancreatitis and pancreatic cancer in pancreatic acinar cells |
| title_sort | nanomolar resveratrol reduces early alterations of pancreatitis and pancreatic cancer in pancreatic acinar cells |
| topic | Pancreatic acinar cells, Pancreatic cancer, Pancreatitis, Resveratrol CCK: cholecystokinin DMEM: Dulbecco´s modified eagle medium |
| url | http://www.sciencedirect.com/science/article/pii/S2667031322000847 |
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