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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.

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-1&beta, secretion and the NLRP3 inflammasome pathway. NLRP3 inflammasome requires two signals, priming to increase the synthesis of NLRP3 and pro-IL-1&beta, 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-1&beta, we show that RWE decreases IL-1 &beta, secretion and gene expression whatever line is used. Moreover, this strong reduction of pro-inflammatory IL-1&beta, is associated with a decrease of NLRP3 and, in J774A, ASC protein expression, which depends on the choice of activator ATP or nigericin.

International audience; Lipid droplets (LD) are now-well recognized as playing a role in cancer progression, however their potential role in chemoresistance remains largely unknown, particularly in colorectal cancer (CRC). We recently highlighted that LD accumulate in CRC cells under the control of lysophosphatidylcholine acyltransferase 2 (LPCAT2) enzyme expression. We also showed that chemotherapy-induced LD accumulation counteracts intrinsic and extrinsic cancer cell death activation.

Numerous epidemiological studies show that various polyphenols may protect against various diseases such as vascular diseases, cancers and inflammatory pathologies. One of the best known is the polyphenol resveratrol which is a trans-3,4’,5-trihydroxystilbene and seems appear to a great interest in the prevention of these pathologies. We have recently shown that resveratrol could prevent carcinogenesis via an anti-inflammatory action through a modulation of miRNA. This inflammation could promote tumoral progression through a modulation of the immune response. Thus, the objectives of this study were to evaluate the potential effect of resveratrol in the immune response in mice with melanoma. Our results highlight that resveratrol modulates differentiation of lymphocytes Th17 which exerts protumoral activity via the interleukin-17 production. Naïve CD4 T cells derived from C57blc/6 mice displayed less capability to differentiate into Th17 cells in vitro after resveratrol treatment. Moreover in mouse model of melanoma (B16F10), resveratrol prevented tumor growth and angiogenesis in an IL-17-dependent manner. This phenomenon could be due to a strong inhibition of the expression of the Th17-specific transcription factor Rorc. This work brings a new mechanism by which resveratrol prevents cancer related inflammation through a modulation of the immune cells and interleukin production., Journal of International Society of Antioxidants in Nutrition & Health, Vol 3, No 4 (2016)

Resveratrol (trans-3,4’,5-trihydroxystilbene), a main wine microcomponent, has been widely described as a chemopreventive agent. Researches performed since the last decades in vitro, in animal models and in (pre)clinical studies have pointed out its pleiotropic health benefits by acting on multiple signaling pathways which go beyond its originally described direct antioxidant activity. One of its potential intracellular targets, as suggested in a neuronal model, is peroxisome proliferators activated receptors (PPARs). In this study, we sought to determine in colorectal cancer cells whether PPARs could be involved in resveratrol-induced cell death. We showed that PPARs agonists strongly decreased tumoral cell proliferation and contributed to resveratrol-induced cell cycle arrest. In addition, PPARgamma agonist rosiglitazone enhanced resveratrol-induced cell death. Inhibition of PPARgamma with its specific antagonist GW9662 or by transient transfection of cancer cells with a dominant-negative PPARgamma mutant abrogated resveratrol-induced effects. Tumor cells death was also potentiated by combining resveratrol with rosiglitazone. Altogether our data show that PPARgamma contributes to resveratrol-induced colon cancer cells death and suggest that the combination of this polyphenol with PPARgamma agonists could be relevant as a new therapeutic approach to treat digestive cancers., Journal of International Society of Antioxidants in Nutrition & Health, Vol 3, No 4 (2016)

The rapid increase in mobile phone use in young people has generated concern about possible health effects of exposure to radiofrequency (RF) and extremely low frequency (ELF) electromagnetic fields (EMF). MOBI-Kids, a multinational case–control study, investigates the potential effects of childhood and adolescent exposure to EMF from mobile communications technologies on brain tumor risk in 14 countries. The study, which aims to include approximately 1,000 brain tumor cases aged 10–24 years and two individually matched controls for each case, follows a common protocol and builds upon the methodological experience of the INTERPHONE study. The design and conduct of a study on EMF exposure and brain tumor risk in young people in a large number of countries is complex and poses methodological challenges.This manuscript discusses the design of MOBI-Kids and describes the challenges and approaches chosen to address them, including: (1) the choice of controls operated for suspected appendicitis, to reduce potential selection bias related to lowresponse rates among population controls; (2) investigating a young study population spanning a relatively wide age range; (3) conducting a large, multinational epidemiological study, while adhering to increasingly stricter ethics requirements; (4) investigating a rare and potentially fatal disease; and (5) assessing exposure to EMF from communication technologies. Our experience in thus far developing and implementing the study protocol indicates that MOBI-Kids is feasible and will generate results that will contribute to the understanding of potential brain tumor risks associated with use of mobile phones and other wireless communications technologies among young people., We would like to thank all of the research assistants and interviewers in the study centers for their enormous efforts to ensure the research leading to these results has received funding from by the European Community's Seventh Framework Programme (FP7/2007-2013) under grant agreement number 22687 3 the MOBI-Kids project. International coordination of the project is partly supported by a grant from the Spanish Ministry of Science and Innovation (MICCIN). Australia: Australian participation in MOBI-Kids is supported by the Australian National Health and Medical Research Council with a five-year research grant (grant number: 546130 and Chief Investigators are: Malcolm R. Sim, Bruce Armstrong, Elizabeth Milne, and Geza Benke). Austria: Austrian participation in MOBI-Kids is partly supported by a grant from the Ministry of Science. Canada: Canadian participation in MOBI-Kids is supported by a university industry partnership grant from the Canadian Institutes of Health Research (CIHR), with the Canadian Wireless Telecommunications Association (CWTA) serving as the industrial partner. CWTA provides technical information on wireless telecommunications in Canada and facilitates access to billing records from Canadian network operators, but has no involvement in the design, conduct, analysis, or interpretation of the MOBI-KIDS study. Health Canada has also provided financial support to facilitate coordination between Canadian and international MOBI-Kids investigators. Daniel Krewski is the Natural Sciences and Engineering Research Council of Canada Chair in Risk Science at the University of Ottawa. France: this project received funds from the French National Agency for Sanitary Safety of Food, Environment and Labour (ANSES, contract FSRF 2008-3), French National Cancer Institute (INCa), Pfizer Foundation and League against cancer. Germany: the German branch of MOBI-Kids is supported by the Federal Office for Radiation Protection. Greece: Greek participation is partially supported by ELKE (Special Account for Research Grants of the National and Kapodistrian University of Athens) and GGET (General Secretariat for Research and Technology). India: MOBI-Kids India is supported by the Board of Research in Nuclear Sciences (BRNS). Italy: Ministry of Health RF-2009-1546284. Japan: Japanese participation in MOBI-Kids is supported by the Ministry of Internal Affairs and Communications. Korea: MOBI-Kids Korea is financially supported by the Ministry of Science, ICT and Future Planning (MSIP), Korea in the ICT R&D Program. New Zealand: MOBI-Kids New Zealand is supported by grants from Cure Kids New Zealand and the New Zealand Health Research Council. Spain: Spanish participation is partially supported by the Spanish Health Research Fund (FIS PI10/02981), the Andalusian Consejeria de Salud (PI-0317/2010) and Conselleria de Sanitat, Generalitat Valenciana under grant number 025/2010. The Netherlands: Dutch participation in MOBI-KIDS is partly supported by The Netherlands Organisation for Health Research and Development (ZonMw) within the program Electromagnetic Fields and Health Research under grant number 85800001, and by the ODAS foundation, a private foundation supporting activities in the field of pediatric oncology and visual disabilities.

IF 4.066; International audience

Endocan also called endothelial cell-specific-molecule-1 is a product of endothelial cells, highly regulated by vascular endothelial growth factor and expressed during the switch between dormant to fast-growing angiogenic tumors. No other molecule is currently known to be a read out of endothelial activation and dysfunction in tumor progression. We here reviewed the present knowledge about endocan that present clinical value as a tissue- and blood- based prognostic and potentially as a companion biomarker in cancer. By immunohistochemistry endocan was shown to be overexpressed into endothelial cells of small and large vessels in lung, kidney and brain tumors. High endocan serum levels were shown to be significantly correlated with the presence of metastasis and with limited survival in kidney and lung cancers. Moreover, endocan release by endothelial cells was in vitro modulated by addition of anti-angiogenic compounds. At a time where biomarkers are hugely needed to improve anti-angiogenic targeted treatments, endocan could be a pertinent biomarker to select patients and/or to clinically monitor the efficacy of cancer drugs. Through its awaited functional applications, endocan appears today as a promising biomarker to access to personalized medicine and to optimize therapy cost / benefit ratio.