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Age-related macular degeneration (AMD) is one of the main causes of deterioration in vision in adults aged 55 and older. In spite of therapies, the progression of the disease is often observed without reverse vision quality. In the present study, we explored whether, in undifferentiated ARPE-19 retinal cells, a disruption of the VEGF receptors (VEGF-R)/caveolin-1 (Cav-1)/protein kinases pathway could be a target for counteracting VEGF secretion. We highlight that Resvega®, a combination of omega-3 fatty acids with an antioxidant, resveratrol, inhibits VEGF-A secretion in vitro by disrupting the dissociation of the VEGF-R2/Cav-1 complex into rafts and subsequently preventing MAPK activation. Moreover, DNA ChIP analysis reveals that this combination prevents the interaction between AP-1 and vegf-a and vegf-r2 gene promoters. By these pathways, Resvega could present a potential interest as nutritional complementation against AMD.
Flavie Courtaut; Alessandra Scagliarini; Virginie Aires; Clarisse Cornebise; Jean-Paul Pais de Barros; Céline Olmiere; Dominique Delmas. VEGF-R2/Caveolin-1 Pathway of Undifferentiated ARPE-19 Retina Cells: A Potential Target as Anti-VEGF-A Therapy in Wet AMD by Resvega, an Omega-3/Polyphenol Combination. International Journal of Molecular Sciences 2021, 22, 6590 .
AMA StyleFlavie Courtaut, Alessandra Scagliarini, Virginie Aires, Clarisse Cornebise, Jean-Paul Pais de Barros, Céline Olmiere, Dominique Delmas. VEGF-R2/Caveolin-1 Pathway of Undifferentiated ARPE-19 Retina Cells: A Potential Target as Anti-VEGF-A Therapy in Wet AMD by Resvega, an Omega-3/Polyphenol Combination. International Journal of Molecular Sciences. 2021; 22 (12):6590.
Chicago/Turabian StyleFlavie Courtaut; Alessandra Scagliarini; Virginie Aires; Clarisse Cornebise; Jean-Paul Pais de Barros; Céline Olmiere; Dominique Delmas. 2021. "VEGF-R2/Caveolin-1 Pathway of Undifferentiated ARPE-19 Retina Cells: A Potential Target as Anti-VEGF-A Therapy in Wet AMD by Resvega, an Omega-3/Polyphenol Combination." International Journal of Molecular Sciences 22, no. 12: 6590.
The multidrug resistance phenotype is a global phenomenon and causes chemotherapy failure in various cancers, such as in uterine sarcomas that have a high mortality rate. To overcome this phenotype, there is growing research interest in developing new treatment strategies. In this study, we highlight the potential of two essential oils from the Apiaceae family, Pituranthos chloranthus (PC) and Teucrium ramosissimum Desf. (TR), to act as chemopreventive and chemosensitizing agents against two uterine sarcoma cell lines, MES-SA and P-gp-overexpressing MES-SA/Dx5 cells. We found that PC and TR were able to inhibit the cell viability of sensitive MES-SA and resistant MES-SA/Dx5 cells by a slight modulation of the cell cycle and its regulators, but also through a significant induction of apoptosis. The molecular mechanism involved both caspase pathways associated with an overproduction of reactive oxygen species (ROS) and mitochondrial membrane depolarization. Very interestingly, the combination of doxorubicin with PC or TR induced a synergism to increase cell death in resistant MES-SA/Dx5 cells and, subsequently, had the benefit of decreasing the resistance index to doxorubicin. These synergistic effects were reinforced by a decrease in P-gp expression and its P-gp adenosine triphosphatase (ATPase) activity, which subsequently led to intracellular doxorubicin accumulation in resistant sarcoma cells.
Aida Lahmar; Aline Mathey; Virginie Aires; Dorra Elgueder; Anne Vejux; Rihab Khlifi; Fairouz Sioud; Leila Chekir-Ghedira; Dominique Delmas. Essential Oils, Pituranthos chloranthus and Teucrium ramosissimum, Chemosensitize Resistant Human Uterine Sarcoma MES-SA/Dx5 Cells to Doxorubicin by Inducing Apoptosis and Targeting P-Glycoprotein. Nutrients 2021, 13, 1719 .
AMA StyleAida Lahmar, Aline Mathey, Virginie Aires, Dorra Elgueder, Anne Vejux, Rihab Khlifi, Fairouz Sioud, Leila Chekir-Ghedira, Dominique Delmas. Essential Oils, Pituranthos chloranthus and Teucrium ramosissimum, Chemosensitize Resistant Human Uterine Sarcoma MES-SA/Dx5 Cells to Doxorubicin by Inducing Apoptosis and Targeting P-Glycoprotein. Nutrients. 2021; 13 (5):1719.
Chicago/Turabian StyleAida Lahmar; Aline Mathey; Virginie Aires; Dorra Elgueder; Anne Vejux; Rihab Khlifi; Fairouz Sioud; Leila Chekir-Ghedira; Dominique Delmas. 2021. "Essential Oils, Pituranthos chloranthus and Teucrium ramosissimum, Chemosensitize Resistant Human Uterine Sarcoma MES-SA/Dx5 Cells to Doxorubicin by Inducing Apoptosis and Targeting P-Glycoprotein." Nutrients 13, no. 5: 1719.
Eye diseases are currently a major public health concern due to the growing number of cases resulting from both an aging of populations and exogenous factors linked to our lifestyles. Thus, many treatments including surgical pharmacological approaches have emerged, and special attention has been paid to prevention, where diet plays a preponderant role. Recently, potential antioxidants such as resveratrol have received much attention as potential tools against various ocular diseases. In this review, we focus on the mechanisms of resveratrol against ocular diseases, in particular age-related macular degeneration, glaucoma, cataract, diabetic retinopathy, and vitreoretinopathy. We analyze, in relation to the different steps of each disease, the resveratrol properties at multiple levels, such as cellular and molecular signaling as well as physiological effects. We show and discuss the relationship to reactive oxygen species, the regulation of inflammatory process, and how resveratrol can prevent ocular diseases through a potential epigenetic action by the activation of sirtuin-1. Lastly, various new forms of resveratrol delivery are emerging at the same time as some clinical trials are raising more questions about the future of resveratrol as a potential tool for prevention or in therapeutic strategies against ocular diseases. More preclinical studies are required to provide further insights into RSV’s potential adjuvant activity.
Dominique Delmas; Clarisse Cornebise; Flavie Courtaut; Jianbo Xiao; Virginie Aires. New Highlights of Resveratrol: A Review of Properties against Ocular Diseases. International Journal of Molecular Sciences 2021, 22, 1295 .
AMA StyleDominique Delmas, Clarisse Cornebise, Flavie Courtaut, Jianbo Xiao, Virginie Aires. New Highlights of Resveratrol: A Review of Properties against Ocular Diseases. International Journal of Molecular Sciences. 2021; 22 (3):1295.
Chicago/Turabian StyleDominique Delmas; Clarisse Cornebise; Flavie Courtaut; Jianbo Xiao; Virginie Aires. 2021. "New Highlights of Resveratrol: A Review of Properties against Ocular Diseases." International Journal of Molecular Sciences 22, no. 3: 1295.
Age-related macular degeneration (AMD) is a degenerative disease of the retina where the molecular mechanism involves the production of vascular endothelial growth factor (VEGF), a factor of poor prognosis of the progression of the disease. Previous studies have shown that resveratrol, a polyphenol of grapevines, can prevent VEGF secretion induced by stress from retinal cells. Considering the fundamental role played by VEGF in development and progression of AMD, we investigate the potential effect of red wine extract (RWE) on VEGF secretion and its signaling pathway in human retinal cells ARPE-19. To examine the effect of RWE in ARPE-19, a quantitative and qualitative analysis of the RWE was performed by HPLC MS/MS. We show for the first time that RWE decreased VEGF-A secretion from ARPE-19 cells and its protein expression in concentration-dependent manner. RWE-induced alteration in VEGF-A production is associated with a down of VEGF-receptor 2 (VEGF-R2) protein expression and its phosphorylated intracytoplasmic domain. Subsequently, the activation of kinase pathway is disturbing and RWE prevents the phosphorylation of MEK and ERK 1/2 in human retinal cells ARPE-19. Finally, this study sheds light on the interest that the use of polyphenolic cocktails could represent in a prevention strategy.
Clarisse Cornebise; Flavie Courtaut; Marie Taillandier-Coindard; Josep Valls-Fonayet; Tristan Richard; David Monchaud; Virginie Aires; Dominique Delmas. Red Wine Extract Inhibits VEGF Secretion and Its Signaling Pathway in Retinal ARPE-19 Cells to Potentially Disrupt AMD. Molecules 2020, 25, 5564 .
AMA StyleClarisse Cornebise, Flavie Courtaut, Marie Taillandier-Coindard, Josep Valls-Fonayet, Tristan Richard, David Monchaud, Virginie Aires, Dominique Delmas. Red Wine Extract Inhibits VEGF Secretion and Its Signaling Pathway in Retinal ARPE-19 Cells to Potentially Disrupt AMD. Molecules. 2020; 25 (23):5564.
Chicago/Turabian StyleClarisse Cornebise; Flavie Courtaut; Marie Taillandier-Coindard; Josep Valls-Fonayet; Tristan Richard; David Monchaud; Virginie Aires; Dominique Delmas. 2020. "Red Wine Extract Inhibits VEGF Secretion and Its Signaling Pathway in Retinal ARPE-19 Cells to Potentially Disrupt AMD." Molecules 25, no. 23: 5564.
The past decade has been marked by an intense scientific interest in the use of compounds or micronutrients of natural origin and their potential effects on human health, both from researchers and industry
Dominique Delmas. Silymarin and Derivatives: From Biosynthesis to Health Benefits. Molecules 2020, 25, 2415 .
AMA StyleDominique Delmas. Silymarin and Derivatives: From Biosynthesis to Health Benefits. Molecules. 2020; 25 (10):2415.
Chicago/Turabian StyleDominique Delmas. 2020. "Silymarin and Derivatives: From Biosynthesis to Health Benefits." Molecules 25, no. 10: 2415.
Silymarin extracted from milk thistle consisting of flavonolignan silybin has shown chemopreventive and chemosensitizing activity against various cancers. The present review summarizes the current knowledge on the potential targets of silymarin against various cancers. Silymarin may play on the system of xenobiotics, metabolizing enzymes (phase I and phase II) to protect normal cells against various toxic molecules or to protect against deleterious effects of chemotherapeutic agents on normal cells. Furthermore, silymarin and its main bioactive compounds inhibit organic anion transporters (OAT) and ATP-binding cassettes (ABC) transporters, thus contributing to counteracting potential chemoresistance. Silymarin and its derivatives play a double role, namely, limiting the progression of cancer cells through different phases of the cycle—thus forcing them to evolve towards a process of cell death—and accumulating cancer cells in a phase of the cell cycle—thus making it possible to target a greater number of tumor cells with a specific anticancer agent. Silymarin exerts a chemopreventive effect by inducing intrinsic and extrinsic pathways and reactivating cell death pathways by modulation of the ratio of proapoptotic/antiapoptotic proteins and synergizing with agonists of death domains receptors. In summary, we highlight how silymarin may act as a chemopreventive agent and a chemosensitizer through multiple pathways.
Dominique Delmas; Jianbo Xiao; Anne Vejux; Virginie Aires. Silymarin and Cancer: A Dual Strategy in Both in Chemoprevention and Chemosensitivity. Molecules 2020, 25, 2009 .
AMA StyleDominique Delmas, Jianbo Xiao, Anne Vejux, Virginie Aires. Silymarin and Cancer: A Dual Strategy in Both in Chemoprevention and Chemosensitivity. Molecules. 2020; 25 (9):2009.
Chicago/Turabian StyleDominique Delmas; Jianbo Xiao; Anne Vejux; Virginie Aires. 2020. "Silymarin and Cancer: A Dual Strategy in Both in Chemoprevention and Chemosensitivity." Molecules 25, no. 9: 2009.
Scope It is well established that immune response and inflammation promote tumoral progression. Immune cells communicate through direct contact or through cytokine secretion, and it is the expression of these mediators and of the pro‐inflammatory status that will tip the balance toward tumor progression or anti‐tumor immunity. We have demonstrated that a red wine extract (RWE) was able to decrease inflammation through its action on the inflammasome complex. In this study, we sought to determine whether an RWE could impact other key actors of inflammation, in particular T helper 17 (Th17) immune cells. Methods and results Using an RWE containing 4.16 g of polyphenols/liter of wine, we showed that RWE decreased colorectal cancer cells (SW620, HCT116, MC38 and CT26) in vitro and that RWE induced a reduction in colorectal tumor growth associated with a decrease in tumor‐infiltrating lymphocytes in vivo. The process of T‐lymphocyte differentiation in Th17 cells was altered by RWE, as revealed by the decrease in the expression of key actors controlling this process, such as signal transducer and activator of transcription 3 and retinoid acid‐related orphan receptorγt. This disruption was associated with an inhibition of inflammatory interleukin 17 secretion. Conclusion The data highlighted the major involvement of Th17 immune cells in the biological effects of an RWE. This article is protected by copyright. All rights reserved
Pauline Chalons; Flavie Courtaut; Emeric Limagne; Fanny Chalmin; Emma Cantos‐Villar; Tristan Richard; Cyril Auger; Philippe Chabert; Valérie Schini‐Kerth; François Ghiringhelli; Virginie Aires; Dominique Delmas. Red Wine Extract Disrupts Th17 Lymphocyte Differentiation in a Colorectal Cancer Context. Molecular Nutrition & Food Research 2020, 64, e1901286 .
AMA StylePauline Chalons, Flavie Courtaut, Emeric Limagne, Fanny Chalmin, Emma Cantos‐Villar, Tristan Richard, Cyril Auger, Philippe Chabert, Valérie Schini‐Kerth, François Ghiringhelli, Virginie Aires, Dominique Delmas. Red Wine Extract Disrupts Th17 Lymphocyte Differentiation in a Colorectal Cancer Context. Molecular Nutrition & Food Research. 2020; 64 (11):e1901286.
Chicago/Turabian StylePauline Chalons; Flavie Courtaut; Emeric Limagne; Fanny Chalmin; Emma Cantos‐Villar; Tristan Richard; Cyril Auger; Philippe Chabert; Valérie Schini‐Kerth; François Ghiringhelli; Virginie Aires; Dominique Delmas. 2020. "Red Wine Extract Disrupts Th17 Lymphocyte Differentiation in a Colorectal Cancer Context." Molecular Nutrition & Food Research 64, no. 11: e1901286.
In spite of chemotherapy and systematic screening for people at risk, the mortality rate of colorectal cancer (CRC) remains consistently high, with 600,000 deaths per year. This low success rate in the treatment of CRC results from many failures associated with high resistance and the risk of metastasis. Therefore, in response to these therapeutic failures, new strategies have been under development for several years aimed at increasing the effect of anticancer compounds and/or at reducing their secondary effects on normal cells, thus enabling the host to better withstand chemotherapy. This study highlights that xanthohumol (Xn) concentrations under the IC50 values were able to induce apoptosis and to enhance the DNA-damage response (DDR). We demonstrate for the first time that Xn exerts its anticancer activity in models of colon cancer through activation of the ataxia telangiectasia mutated (ATM) pathway. Subsequently, the ability of Xn to restore DNA damage in CRC cells can sensitize them to anticancer agents such as SN38 (7-ethyl-10-hydroxycamptothecin) used in chemotherapy.
Alessandra Scagliarini; Aline Mathey; Virginie Aires; Dominique Delmas. Xanthohumol, a Prenylated Flavonoid from Hops, Induces DNA Damages in Colorectal Cancer Cells and Sensitizes SW480 Cells to the SN38 Chemotherapeutic Agent. Cells 2020, 9, 932 .
AMA StyleAlessandra Scagliarini, Aline Mathey, Virginie Aires, Dominique Delmas. Xanthohumol, a Prenylated Flavonoid from Hops, Induces DNA Damages in Colorectal Cancer Cells and Sensitizes SW480 Cells to the SN38 Chemotherapeutic Agent. Cells. 2020; 9 (4):932.
Chicago/Turabian StyleAlessandra Scagliarini; Aline Mathey; Virginie Aires; Dominique Delmas. 2020. "Xanthohumol, a Prenylated Flavonoid from Hops, Induces DNA Damages in Colorectal Cancer Cells and Sensitizes SW480 Cells to the SN38 Chemotherapeutic Agent." Cells 9, no. 4: 932.
Despite major advances in the last 10 years, whether in terms of prevention or treatment, the 5 year survival rate remains relatively low for a large number of cancers. These therapeutic failures can be the consequence of several factors associated with the cellular modifications or with the host by itself, especially for some anticancer drugs such as cisplatin, which induces a nephrotoxicity. In the strategy of research for active molecules capable both of exerting a protective action against the deleterious effects of cisplatin and exerting a chemosensitizing action with regard to cancer cells, we tested the potential effects of Ephedra alata Decne extract (E.A.) rich in polyphenolic compounds towards a 4T1 breast cancer model in vitro and in vivo. We showed that E.A. extract inhibited cell viability of 4T1 breast cancer cells and induced apoptosis in a caspase-dependent manner, which involved intrinsic pathways. Very interestingly, we observed a synergic antiproliferative and pro-apoptotic action with cisplatin. These events were associated with a strong decrease of breast tumor growth in mice treated with an E.A./cisplatin combination and simultaneously with a decrease of hepato- and nephrotoxicities of cisplatin.
Fairouz Sioud; Souheila Amor; Imène Ben Toumia; Aida Lahmar; Virginie Aires; Leila Chekir-Ghedira; Dominique Delmas. A New Highlight of Ephedra alata Decne Properties as Potential Adjuvant in Combination with Cisplatin to Induce Cell Death of 4T1 Breast Cancer Cells In Vitro and In Vivo. Cells 2020, 9, 362 .
AMA StyleFairouz Sioud, Souheila Amor, Imène Ben Toumia, Aida Lahmar, Virginie Aires, Leila Chekir-Ghedira, Dominique Delmas. A New Highlight of Ephedra alata Decne Properties as Potential Adjuvant in Combination with Cisplatin to Induce Cell Death of 4T1 Breast Cancer Cells In Vitro and In Vivo. Cells. 2020; 9 (2):362.
Chicago/Turabian StyleFairouz Sioud; Souheila Amor; Imène Ben Toumia; Aida Lahmar; Virginie Aires; Leila Chekir-Ghedira; Dominique Delmas. 2020. "A New Highlight of Ephedra alata Decne Properties as Potential Adjuvant in Combination with Cisplatin to Induce Cell Death of 4T1 Breast Cancer Cells In Vitro and In Vivo." Cells 9, no. 2: 362.
Modulation of the inflammatory response is one of the major issues of the 21st century due to its importance in the occurrence of various pathologies (cancer, autoimmune diseases, degenerative diseases) and their progression over time. Whether acute or chronic, the inflammatory response is directly related to the immune response through different subtypes of T lymphocytes. In addition, among the compounds capable of modulating the cells of the immune system, resveratrol, a polyphenol with pleiotropic biological properties, seems to be a good candidate. Indeed, resveratrol is able to alter the immune response by modulating the process of lymphocyte differentiation and subsequently diminishing the inflammatory-associated response. More specifically, thanks to its ability to act as a sirtuin-1 agonist, it can deacetylate the transcription factor STAT3 and alter nuclear factors essential to the process of lymphocyte differentiation. We present and discuss these different aspects in relation to various pathologies and how the alteration of the ratios between the different lymphocyte subtypes by resveratrol is an important element to take into account when studying its anti-inflammatory and immunomodulatory properties.
Dominique Delmas; Emeric Limagne; François Ghiringhelli; Virginie Aires. Immune Th17 lymphocytes play a critical role in the multiple beneficial properties of resveratrol. Food and Chemical Toxicology 2019, 137, 111091 .
AMA StyleDominique Delmas, Emeric Limagne, François Ghiringhelli, Virginie Aires. Immune Th17 lymphocytes play a critical role in the multiple beneficial properties of resveratrol. Food and Chemical Toxicology. 2019; 137 ():111091.
Chicago/Turabian StyleDominique Delmas; Emeric Limagne; François Ghiringhelli; Virginie Aires. 2019. "Immune Th17 lymphocytes play a critical role in the multiple beneficial properties of resveratrol." Food and Chemical Toxicology 137, no. : 111091.
Resveratrol has been proposed to prevent tumor growth and the different steps of carcinogenesis; nevertheless, these biological effects are sometimes discordant between different cell types. Several hypotheses and works have suggested that the metabolism of resveratrol could be at the origin of a different cellular response. We show here, using colorectal tumor cell lines, that the biological effects of RSV result mainly from its carriage by carriers of the superfamily of ABC transporter, i.e., P-gP, MRP, or BCRP. Using cell lines overexpressing these different transporters, we have been able to highlight the importance of P-gP in the response of cells to RSV. These results were confirmed by invalidating the gene coding for P-gP, which restored the sensitivity of colorectal cells resistant to the polyphenol. Subsequently, the status of P-glycoprotein expression is an important element to be taken into consideration in the cytotoxic activity of resveratrol in colorectal cancer cells.
Virginie Aires; Didier J Colin; Agnès Doreau; Attilio Di Pietro; Jean-Marie Heydel; Yves Artur; Norbert Latruffe; Dominique Delmas. P-Glycoprotein 1 Affects Chemoactivities of Resveratrol against Human Colorectal Cancer Cells. Nutrients 2019, 11, 2098 .
AMA StyleVirginie Aires, Didier J Colin, Agnès Doreau, Attilio Di Pietro, Jean-Marie Heydel, Yves Artur, Norbert Latruffe, Dominique Delmas. P-Glycoprotein 1 Affects Chemoactivities of Resveratrol against Human Colorectal Cancer Cells. Nutrients. 2019; 11 (9):2098.
Chicago/Turabian StyleVirginie Aires; Didier J Colin; Agnès Doreau; Attilio Di Pietro; Jean-Marie Heydel; Yves Artur; Norbert Latruffe; Dominique Delmas. 2019. "P-Glycoprotein 1 Affects Chemoactivities of Resveratrol against Human Colorectal Cancer Cells." Nutrients 11, no. 9: 2098.
Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide. Phospholipids are now well-recognised players in tumour progression. Their metabolic tissue alterations can be associated with plasmatic modifications. The aim of this study was to evaluate the potential of the plasma phospholipid profile as a risk and prognostic biomarker in HCC. Ninety cirrhotic patients with (cases) or without HCC (controls) were studied after matching for inclusion centre, age, gender, virus infection, cirrhosis duration and Child-Pugh grade. High-performance liquid chromatography coupled with tandem-mass spectrometry was used to quantify the main species of seven categories of phospholipids in plasma. Elevated concentrations of phosphatidylcholine (PC) 16:0/16:1 (p=0.0180), PC 16:0/16:0 (p=0.0327), PC 16:0/18:1 (p=0.0264) and sphingomyelin (SM) 18:2/24:1 (p=0.0379) and low concentrations of lysophosphatidylcholine 20:4 (0.0093) and plasmalogen-phosphatidylethanolamine (pPE) 16:0/20:4 (p=0.0463), pPE 18:0/20:4 (p=0.0077), pPE 18:0/20:5 (p=0.0163), pPE 18:0/20:3 (p=0.0463) discriminated HCC patients from cirrhotic controls. Two ceramide species were associated with increased HCC risk of death while lysophospholipids, a polyunsaturated phosphatidylinositol, some PC and SM species were associated with low risk of death in HCC patients in 1 and/or 3 years. This study identified phospholipid profiles related to HCC risk in liver cirrhotic patients and showed for the first time the potential of some phospholipids in predicting HCC patient mortality.
Alexia Karen Cotte; Vanessa Cottet; Virginie Aires; Thomas Mouillot; Maud Rizk; Sandrine Vinault; Christine Binquet; Jean-Paul Pais De Barros; Patrick Hillon; Dominique Delmas. Phospholipid profiles and hepatocellular carcinoma risk and prognosis in cirrhotic patients. Oncotarget 2019, 10, 2161 -2172.
AMA StyleAlexia Karen Cotte, Vanessa Cottet, Virginie Aires, Thomas Mouillot, Maud Rizk, Sandrine Vinault, Christine Binquet, Jean-Paul Pais De Barros, Patrick Hillon, Dominique Delmas. Phospholipid profiles and hepatocellular carcinoma risk and prognosis in cirrhotic patients. Oncotarget. 2019; 10 (22):2161-2172.
Chicago/Turabian StyleAlexia Karen Cotte; Vanessa Cottet; Virginie Aires; Thomas Mouillot; Maud Rizk; Sandrine Vinault; Christine Binquet; Jean-Paul Pais De Barros; Patrick Hillon; Dominique Delmas. 2019. "Phospholipid profiles and hepatocellular carcinoma risk and prognosis in cirrhotic patients." Oncotarget 10, no. 22: 2161-2172.
Inflammation has been described as an initiator event of major diseases with significant impacts in terms of public health including in cardiovascular disease, autoimmune disorders, eye diseases, age-related diseases, and the occurrence of cancers. A preventive action to reduce the key processes leading to inflammation could be an advantageous approach to reducing these associated pathologies. Many studies have reported the value of polyphenols such as resveratrol in counteracting pro-inflammatory cytokines. We have previously shown the potential of red wine extract (RWE) and the value of its qualitative and quantitative polyphenolic composition to prevent the carcinogenesis process. In this study, we addressed a new effect of RWE in inflammation through a modulation of IL-1β secretion and the NLRP3 inflammasome pathway. NLRP3 inflammasome requires two signals, priming to increase the synthesis of NLRP3 and pro-IL-1β proteins and activation, which activates NLRP3. Inflammasome formation is triggered by a range of substances such as lipopolysaccharide (LPS). Using two different macrophages, one of which does not express the adaptor protein ASC (apoptosis-associated speck-like protein containing a CARD), which is essential to form active inflammasome complexes that produce IL-1β, we show that RWE decreases IL-1 β secretion and gene expression whatever line is used. Moreover, this strong reduction of pro-inflammatory IL-1β is associated with a decrease of NLRP3 and, in J774A, ASC protein expression, which depends on the choice of activator ATP or nigericin.
Pauline Chalons; Souheila Amor; Flavie Courtaut; Emma Cantos-Villar; Tristan Richard; Cyril Auger; Philippe Chabert; Valérie Schni-Kerth; Virginie Aires; Dominique Delmas. Study of Potential Anti-Inflammatory Effects of Red Wine Extract and Resveratrol through a Modulation of Interleukin-1-Beta in Macrophages. Nutrients 2018, 10, 1856 .
AMA StylePauline Chalons, Souheila Amor, Flavie Courtaut, Emma Cantos-Villar, Tristan Richard, Cyril Auger, Philippe Chabert, Valérie Schni-Kerth, Virginie Aires, Dominique Delmas. Study of Potential Anti-Inflammatory Effects of Red Wine Extract and Resveratrol through a Modulation of Interleukin-1-Beta in Macrophages. Nutrients. 2018; 10 (12):1856.
Chicago/Turabian StylePauline Chalons; Souheila Amor; Flavie Courtaut; Emma Cantos-Villar; Tristan Richard; Cyril Auger; Philippe Chabert; Valérie Schni-Kerth; Virginie Aires; Dominique Delmas. 2018. "Study of Potential Anti-Inflammatory Effects of Red Wine Extract and Resveratrol through a Modulation of Interleukin-1-Beta in Macrophages." Nutrients 10, no. 12: 1856.
Wine has been popular worldwide for many centuries and currently remains an important component of our diet. Scientific interest in wine and its health effects has grown considerably since the 1990s with the emergence of the “French Paradox” concept, correlating moderate wine consumption, a characteristic of the Mediterranean diet, and low incidence of coronary heart diseases. Since then, the positive effects on health, health promotion, disease prevention, and disease prognosis of moderate wine consumption, in particular red wine, have been attributed to its polyphenolic compounds such as resveratrol, quercetin, and other flavonoids acting as antioxidants. Several epidemiological, in vivo and in vitro, studies have reported that moderate red wine or red wine polyphenolic extract consumption may be active in the prevention and treatment of chronic diseases such as cardiovascular disease, metabolic syndrome, degenerative pathologies, and cancer. The aim of this review is to summarize the current findings about the effects of red wine polyphenols on cancer and to discuss how the polyphenolic composition of red wine may influence its chemopreventive properties.
Souheila Amor; Pauline Châlons; Virginie Aires; Dominique Delmas. Polyphenol Extracts from Red Wine and Grapevine: Potential Effects on Cancers. Diseases 2018, 6, 106 .
AMA StyleSouheila Amor, Pauline Châlons, Virginie Aires, Dominique Delmas. Polyphenol Extracts from Red Wine and Grapevine: Potential Effects on Cancers. Diseases. 2018; 6 (4):106.
Chicago/Turabian StyleSouheila Amor; Pauline Châlons; Virginie Aires; Dominique Delmas. 2018. "Polyphenol Extracts from Red Wine and Grapevine: Potential Effects on Cancers." Diseases 6, no. 4: 106.
Very recently, we have produced new resveratrol derived compounds, especially labruscol by culture of elicited grapevine cell suspensions (Vitis labrusca L.). This new polyphenolic oligomer could function as cancer chemopreventive agent in similar manner of resveratrol. In this study, we have determined the efficiency of resveratrol, ε-viniferin and the labruscol on human melanoma cell with or without metastatic phenotype. Our results show a differential activity of the three compounds where the resveratrol remains the polyphenolic compound with the most effective action compared to other oligomers. These three compounds block cell cycle of melanoma cells in S phase by modulating key regulators of cell cycle i.e. cyclins A, E, D1 and their cyclin–dependent kinases 1 and 2. These effects are associated with an increase of cell death while these compounds have no cytotoxic action on normal human dermal fibroblasts.
Laetitia Nivelle; Virginie Aires; Damien Rioult; Laurent Martiny; Michel Tarpin; Dominique Delmas. Molecular analysis of differential antiproliferative activity of resveratrol, epsilon viniferin and labruscol on melanoma cells and normal dermal cells. Food and Chemical Toxicology 2018, 116, 323 -334.
AMA StyleLaetitia Nivelle, Virginie Aires, Damien Rioult, Laurent Martiny, Michel Tarpin, Dominique Delmas. Molecular analysis of differential antiproliferative activity of resveratrol, epsilon viniferin and labruscol on melanoma cells and normal dermal cells. Food and Chemical Toxicology. 2018; 116 ():323-334.
Chicago/Turabian StyleLaetitia Nivelle; Virginie Aires; Damien Rioult; Laurent Martiny; Michel Tarpin; Dominique Delmas. 2018. "Molecular analysis of differential antiproliferative activity of resveratrol, epsilon viniferin and labruscol on melanoma cells and normal dermal cells." Food and Chemical Toxicology 116, no. : 323-334.
Lipid droplet (LD) accumulation is a now well-recognised hallmark of cancer. However, the significance of LD accumulation in colorectal cancer (CRC) biology is incompletely understood under chemotherapeutic conditions. Since drug resistance is a major obstacle to treatment success, we sought to determine the contribution of LD accumulation to chemotherapy resistance in CRC. Here we show that LD content of CRC cells positively correlates with the expression of lysophosphatidylcholine acyltransferase 2 (LPCAT2), an LD-localised enzyme supporting phosphatidylcholine synthesis. We also demonstrate that LD accumulation drives cell-death resistance to 5-fluorouracil and oxaliplatin treatments both in vitro and in vivo. Mechanistically, LD accumulation impairs caspase cascade activation and ER stress responses. Notably, droplet accumulation is associated with a reduction in immunogenic cell death and CD8 T cell infiltration in mouse tumour grafts and metastatic tumours of CRC patients. Collectively our findings highlight LPCAT2-mediated LD accumulation as a druggable mechanism to restore CRC cell sensitivity.
Alexia Karen Cotte; Virginie Aires; Maxime Fredon; Emeric Limagne; Valentin Derangère; Marion Thibaudin; Etienne Humblin; Alessandra Scagliarini; Jean-Paul Pais De Barros; Patrick Hillon; Francois Ghiringhelli; Dominique Delmas. Lysophosphatidylcholine acyltransferase 2-mediated lipid droplet production supports colorectal cancer chemoresistance. Nature Communications 2018, 9, 322 .
AMA StyleAlexia Karen Cotte, Virginie Aires, Maxime Fredon, Emeric Limagne, Valentin Derangère, Marion Thibaudin, Etienne Humblin, Alessandra Scagliarini, Jean-Paul Pais De Barros, Patrick Hillon, Francois Ghiringhelli, Dominique Delmas. Lysophosphatidylcholine acyltransferase 2-mediated lipid droplet production supports colorectal cancer chemoresistance. Nature Communications. 2018; 9 (1):322.
Chicago/Turabian StyleAlexia Karen Cotte; Virginie Aires; Maxime Fredon; Emeric Limagne; Valentin Derangère; Marion Thibaudin; Etienne Humblin; Alessandra Scagliarini; Jean-Paul Pais De Barros; Patrick Hillon; Francois Ghiringhelli; Dominique Delmas. 2018. "Lysophosphatidylcholine acyltransferase 2-mediated lipid droplet production supports colorectal cancer chemoresistance." Nature Communications 9, no. 1: 322.
A new resveratrol dimer (1) called labruscol, has been purified by centrifugal partition chromatography of a crude ethyl acetate stilbene extract obtained from elicited grapevine cell suspensions of Vitis labrusca L. cultured in a 14-liter stirred bioreactor. One dimensional (1D) and two dimensional (2D) nuclear magnetic resonance (NMR) analyses including 1H, 13C, heteronuclear single-quantum correlation (HSQC), heteronuclear multiple bond correlation (HMBC), and correlation spectroscopy (COSY) as well as high-resolution electrospray ionisation mass spectrometry (HR-ESI-MS) were used to characterize this compound and to unambiguously identify it as a new stilbene dimer, though its relative stereochemistry remained unsolved. Labruscol was recovered as a pure compound (>93%) in sufficient amounts (41 mg) to allow assessment of its biological activity (cell viability, cell invasion and apoptotic activity) on two different cell lines, including one human skin melanoma cancer cell line HT-144 and a healthy human dermal fibroblast (HDF) line. This compound induced almost 100% of cell viability inhibition in the cancer line at a dose of 100 μM within 72 h of treatment. However, at all tested concentrations and treatment times, resveratrol displayed an inhibition of the cancer line viability higher than that of labruscol in the presence of fetal bovine serum. Both compounds also showed differential activities on healthy and cancer cell lines. Finally, labruscol at a concentration of 1.2 μM was shown to reduce cell invasion by 40%, although no similar activity was observed with resveratrol. The cytotoxic activity of this newly-identified dimer is discussed.
Laetitia Nivelle; Jane Hubert; Eric Courot; Nicolas Borie; Jean-Hugues Renault; Jean-Marc Nuzillard; Dominique Harakat; Christophe Clément; Laurent Martiny; Dominique Delmas; Philippe Jeandet; Michel Tarpin. Cytotoxicity of Labruscol, a New Resveratrol Dimer Produced by Grapevine Cell Suspensions, on Human Skin Melanoma Cancer Cell Line HT-144. Molecules 2017, 22, 1940 .
AMA StyleLaetitia Nivelle, Jane Hubert, Eric Courot, Nicolas Borie, Jean-Hugues Renault, Jean-Marc Nuzillard, Dominique Harakat, Christophe Clément, Laurent Martiny, Dominique Delmas, Philippe Jeandet, Michel Tarpin. Cytotoxicity of Labruscol, a New Resveratrol Dimer Produced by Grapevine Cell Suspensions, on Human Skin Melanoma Cancer Cell Line HT-144. Molecules. 2017; 22 (11):1940.
Chicago/Turabian StyleLaetitia Nivelle; Jane Hubert; Eric Courot; Nicolas Borie; Jean-Hugues Renault; Jean-Marc Nuzillard; Dominique Harakat; Christophe Clément; Laurent Martiny; Dominique Delmas; Philippe Jeandet; Michel Tarpin. 2017. "Cytotoxicity of Labruscol, a New Resveratrol Dimer Produced by Grapevine Cell Suspensions, on Human Skin Melanoma Cancer Cell Line HT-144." Molecules 22, no. 11: 1940.
In the present study, resveratrol and various oligomeric derivatives were obtained from a 14 L bioreactor culture of elicited grapevine cell suspensions (Vitis labrusca L.). The crude ethyl acetate stilbene extract obtained from the culture medium was fractionated by centrifugal partition chromatography (CPC) using a gradient elution method and the major stilbenes contained in the fractions were subsequently identified by using a 13C-NMR-based dereplication procedure and further 2D NMR analyses including HSQC, HMBC, and COSY. Beside δ-viniferin (2), leachianol F (4) and G (4′), four stilbenes (resveratrol (1), ε-viniferin (5), pallidol (3) and a newly characterized dimer (6)) were recovered as pure compounds in sufficient amounts to allow assessment of their biological activity on the cell growth of three different cell lines, including two human skin malignant melanoma cancer cell lines (HT-144 and SKMEL-28) and a healthy human dermal fibroblast HDF line. Among the dimers obtained in this study, the newly characterized resveratrol dimer (6) has never been described in nature and its biological potential was evaluated here for the first time. ε-viniferin as well as dimer (6) showed IC50 values on the three tested cell lines lower than the ones exerted by resveratrol and pallidol. However, activities of the first two compounds were significantly decreased in the presence of fetal bovine serum although that of resveratrol and pallidol was not. The differential tumor activity exerted by resveratrol on healthy and cancer lines was also discussed.
Laetitia Nivelle; Jane Hubert; Eric Courot; Philippe Jeandet; Aziz Aziz; Jean-Marc Nuzillard; Jean-Hugues Renault; Christophe Clément; Laurent Martiny; Dominique Delmas; Michel Tarpin. Anti-Cancer Activity of Resveratrol and Derivatives Produced by Grapevine Cell Suspensions in a 14 L Stirred Bioreactor. Molecules 2017, 22, 474 .
AMA StyleLaetitia Nivelle, Jane Hubert, Eric Courot, Philippe Jeandet, Aziz Aziz, Jean-Marc Nuzillard, Jean-Hugues Renault, Christophe Clément, Laurent Martiny, Dominique Delmas, Michel Tarpin. Anti-Cancer Activity of Resveratrol and Derivatives Produced by Grapevine Cell Suspensions in a 14 L Stirred Bioreactor. Molecules. 2017; 22 (3):474.
Chicago/Turabian StyleLaetitia Nivelle; Jane Hubert; Eric Courot; Philippe Jeandet; Aziz Aziz; Jean-Marc Nuzillard; Jean-Hugues Renault; Christophe Clément; Laurent Martiny; Dominique Delmas; Michel Tarpin. 2017. "Anti-Cancer Activity of Resveratrol and Derivatives Produced by Grapevine Cell Suspensions in a 14 L Stirred Bioreactor." Molecules 22, no. 3: 474.
State of the art. Osteoarthritis (OA) is a chronic articular disease characterized by cartilage degradation and osteophyte formation. OA physiopathology is multifactorial and involves mechanical and hereditary factors. So far, there is neither preventive medicine to delay cartilage breakdown nor curative treatment. Objectives. To investigate pro-inflammatory paracrine interactions between human primary chondrocytes and macrophages following interleukin-1-β (IL-1β) treatment; to evaluate the molecular mechanism responsible for the inhibitory effect of resveratrol. Results. The activation of NF-κB in chondrocytes by IL-1β induced IL-6 secretion. The latter will then activate STAT3 protein in macrophages. Moreover, STAT3 was able to positively regulate IL-6 secretion, as confirmed by the doubling level of IL-6 in the coculture compared to macrophage monoculture. These experiments confirm the usefulness of the coculture model in the inflammatory arthritis-linked process as a closer biological situation to the synovial joint than separated chondrocytes and macrophages. Il also demonstrated the presence of an inflammatory amplification loop induced by IL-1β. Resveratrol showed a strong inhibitory effect on the pro-inflammatory marker secretion. The decrease of IL-6 secretion is dependent on the NFκB inhibition in the chondrocytes. Such reduction of the IL-6 level can limit STAT3 activation in the macrophages, leading to the interruption of the inflammatory amplification loop. Conclusion. These results increase our understanding of the anti-inflammatory actions of resveratrol and open new potential approaches to prevent and treat osteoarthritis.
Emeric Limagne; Allan Lançon; Dominique Delmas; Mustapha Cherkaoui-Malki; Norbert Latruffe. Resveratrol Interferes with IL1-β-Induced Pro-Inflammatory Paracrine Interaction between Primary Chondrocytes and Macrophages. Nutrients 2016, 8, 280 .
AMA StyleEmeric Limagne, Allan Lançon, Dominique Delmas, Mustapha Cherkaoui-Malki, Norbert Latruffe. Resveratrol Interferes with IL1-β-Induced Pro-Inflammatory Paracrine Interaction between Primary Chondrocytes and Macrophages. Nutrients. 2016; 8 (5):280.
Chicago/Turabian StyleEmeric Limagne; Allan Lançon; Dominique Delmas; Mustapha Cherkaoui-Malki; Norbert Latruffe. 2016. "Resveratrol Interferes with IL1-β-Induced Pro-Inflammatory Paracrine Interaction between Primary Chondrocytes and Macrophages." Nutrients 8, no. 5: 280.
Further advances in understanding the mechanism of action of resveratrol and its application require new analogs to identify the structural determinants for the cell proliferation inhibition potency. Therefore, we synthesized new trans-resveratrol derivatives by using the Wittig and Heck methods, thus modifying the hydroxylation and methoxylation patterns of the parent molecule. Moreover, we also synthesized new ferrocenylstilbene analogs by using an original protective group in the Wittig procedure. By performing cell proliferation assays we observed that the resveratrol derivatives show inhibition on the human colorectal tumor SW480 cell line. On the other hand, cell viability/cytotoxicity assays showed a weaker effects on the human hepatoblastoma HepG2 cell line. Importantly, the lack of effect on non-tumor cells (IEC18 intestinal epithelium cells) demonstrates the selectivity of these molecules for cancer cells. Here, we show that the numbers and positions of hydroxy and methoxy groups are crucial for the inhibition efficacy. In addition, the presence of at least one phenolic group is essential for the antitumoral activity. Moreover, in the series of ferrocenylstilbene analogs, the presence of a hidden phenolic function allows for a better solubilization in the cellular environment and significantly increases the antitumoral activity.
Malik Chalal; Dominique Delmas; Philippe Meunier; Norbert Latruffe; Dominique Vervandier-Fasseur. Inhibition of Cancer Derived Cell Lines Proliferation by Synthesized Hydroxylated Stilbenes and New Ferrocenyl-Stilbene Analogs. Comparison with Resveratrol. Molecules 2014, 19, 7850 -7868.
AMA StyleMalik Chalal, Dominique Delmas, Philippe Meunier, Norbert Latruffe, Dominique Vervandier-Fasseur. Inhibition of Cancer Derived Cell Lines Proliferation by Synthesized Hydroxylated Stilbenes and New Ferrocenyl-Stilbene Analogs. Comparison with Resveratrol. Molecules. 2014; 19 (6):7850-7868.
Chicago/Turabian StyleMalik Chalal; Dominique Delmas; Philippe Meunier; Norbert Latruffe; Dominique Vervandier-Fasseur. 2014. "Inhibition of Cancer Derived Cell Lines Proliferation by Synthesized Hydroxylated Stilbenes and New Ferrocenyl-Stilbene Analogs. Comparison with Resveratrol." Molecules 19, no. 6: 7850-7868.