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Sophie Raynal

Bio: Sophie Raynal is an academic researcher from University of Paris. The author has contributed to research in topics: G protein-coupled receptor & Receptor. The author has an hindex of 2, co-authored 3 publications receiving 18 citations.

Papers
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Journal ArticleDOI
TL;DR: Results show that a new 2-oxindole fluorinated derivative exerts potent in vivo antitumor actions against prostate cancer cells, indicating a promising clinical therapeutic strategy for the treatment of androgen-independent prostate cancer.
Abstract: The key metabolic sensor adenosine monophosphate-dependent kinase (AMPK) has emerged as a promising therapeutic target for cancer prevention and treatment. Besides its role in energy homeostasis, AMPK blocks cell cycle, regulates autophagy and suppresses the anabolic processes required for rapid cell growth. AMPK is especially relevant in prostate cancer in which activation of lipogenic pathways correlate with tumor progression and aggressiveness. This study reports the discovery of a new series of 2-oxindole derivatives whose AMPK modulatory ability, as well as the antitumoral profile in prostate cancer cells, was evaluated. One of the assayed compounds, compound 8c, notably activated AMPK in cultured PC-3, DU145 and LNCaP prostate cancer cells. Likewise, compound 8c caused PC-3, DU145 and LNCaP cells viability inhibition. Selective knocking down of α1 or α2 isoforms as well as in vitro assays using human recombinant α1β1γ1 or α2β1γ1 AMPK isoforms revealed that compound 8c exhibit preference for AMPKα1. Consistent with efficacy at the cellular level, compound 8c was potent in suppressing the growth of PC-3 xenograft tumors. In conclusion, our results show that a new 2-oxindole fluorinated derivative exerts potent in vivo antitumor actions against prostate cancer cells, indicating a promising clinical therapeutic strategy for the treatment of androgen-independent prostate cancer.

14 citations

Posted ContentDOI
10 Apr 2020-bioRxiv
TL;DR: The possibility to activate the Mas receptor with a safe steroid molecule is consistent with the pleiotropic pharmacological effects of ecdysteroids in mammals and indeed this mechanism may explain the close similarity between angiotensin-(1-7) and 20E effects.
Abstract: 20-Hydroxyecdysone (20E) is a steroid hormone that plays a key role in insect development through nuclear ecdysone receptors (EcRs) and at least one membrane GPCR receptor (DopEcR) and displays numerous pharmacological effects in mammals. However, its mechanism of action is still debated, involving either an unidentified GPCR or the estrogen ER receptor. The goal of our study was to better understand 20E mechanism of action. A mouse myoblast cell line (C2C12) and the gene expression of myostatin (a negative regulator of muscle growth) was used as a reporter system of anabolic activity. Experiments using protein-bound 20E established the involvement of a membrane receptor. 20E-like effects were also observed with Angiotensin-(1-7), the endogenous ligand of Mas. Additionally, the effect on myostatin gene expression was abolished by Mas receptor knock-down using small interfering RNA (siRNA) or pharmacological inhibitors. 17-Estradiol (E2) also inhibited myostatin gene expression, but protein-bound E2 was inactive, and E2 activity was not abolished by angiotensin-(1-7) antagonists. A mechanism involving cooperation between Mas receptor and a membrane-bound palmitoylated estrogen receptor is proposed.The possibility to activate the Mas receptor with a safe steroid molecule is consistent with the pleiotropic pharmacological effects of ecdysteroids in mammals and indeed this mechanism may explain the close similarity between angiotensin-(1-7) and 20E effects. Our findings open a lot of possible therapeutic developments by stimulating the protective arm of the renin-angiotensin-aldosterone system (RAAS) with 20E.

11 citations

Patent
20 May 2015
TL;DR: L'invention permet egalement d'ameliorer la qualite musculaire chez les mammiferes obeses et traiter et/ou prevenir l'obesite et ses complications and pathologies associees, avantageusement le diabete de type 2 et le syndrome metabolique.
Abstract: La presente invention concerne des composes chimiques et leur utilisation therapeutique, en particulier pour l'amelioration de la qualite musculaire chez les mammiferes. Plus particulierement l'invention permet d'ameliorer la qualite musculaire des mammiferes sarcopeniques et de traiter et/ou prevenir la sarcopenie et en particulier l'obesite sarcopenique, ses complications et/ou pathologies associees telles que la perte de force, de masse musculaire, de performances et capacite physiques et de mobilite. L'invention permet egalement d'ameliorer la qualite musculaire chez les mammiferes obeses et traiter et/ou prevenir l'obesite et ses complications et/ou pathologies associees, avantageusement le diabete de type 2 et le syndrome metabolique.

Cited by
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Journal ArticleDOI
TL;DR: In this paper, the authors provide a description of the general chemistry based on existing corresponding structureactivity relationships (SARs) and compile all recent developmentary studies on oxindole-derived compounds as a successful pharmaceutical agent.

75 citations

Journal ArticleDOI
TL;DR: In this paper, a review summarises recent advances in the development of oxindole-based kinase inhibitors, including 3-alkenyl oxindoles and spirooxindoles.

38 citations

Journal ArticleDOI
10 Jun 2020-Cells
TL;DR: It is demonstrated that long-term androgen signal depletion of prostate LNCaP cells induced a neuroendocrine phenotype followed by re-differentiation towards a “stem-like” state through AMPK, and docetaxel sensitivity was restored in stem-like AMPK-transfected cells.
Abstract: In the past few years, cell plasticity has emerged as a mode of targeted therapy evasion in prostate adenocarcinoma. When exposed to anticancer therapies, tumor cells may switch into a different histological subtype, such as the neuroendocrine phenotype which is associated with treatment failure and a poor prognosis. In this study, we demonstrated that long-term androgen signal depletion of prostate LNCaP cells induced a neuroendocrine phenotype followed by re-differentiation towards a “stem-like” state. LNCaP cells incubated for 30 days in charcoal-stripped medium or with the androgen receptor antagonist 2-hydroxyflutamide developed neuroendocrine morphology and increased the expression of the neuroendocrine markers βIII-tubulin and neuron specific enolase (NSE). When cells were incubated for 90 days in androgen-depleted medium, they grew as floating spheres and had enhanced expression of the stem cell markers CD133, ALDH1A1, and the transporter ABCB1A. Additionally, the pluripotent transcription factors Nanog and Oct4 and the angiogenic factor VEGF were up-regulated while the expression of E-cadherin was inhibited. Cell viability revealed that those cells were resistant to docetaxel and 2-hidroxyflutamide. Mechanistically, androgen depletion induced the decrease in AMP-activated kinase (AMPK) expression and activation and stabilization of the hypoxia-inducible factor HIF-1α. Overexpression of AMPK in the stem-like cells decreased the expression of stem markers as well as that of HIF-1α and VEGF while it restored the levels of E-cadherin and PGC-1α. Most importantly, docetaxel sensitivity was restored in stem-like AMPK-transfected cells. Our model provides a new regulatory mechanism of prostate cancer plasticity through AMPK that is worth exploring.

30 citations

Journal ArticleDOI
TL;DR: There is growing interest in the pharmaceutical and medical applications of 20-hydroxyecdysone (20E), a polyhydroxylated steroid which naturally occurs in low but very significant amounts in invertebrates, and in certain plant species, where it is believed to contribute to the deterrence of invertebrate predators as mentioned in this paper.
Abstract: There is growing interest in the pharmaceutical and medical applications of 20-hydroxyecdysone (20E), a polyhydroxylated steroid which naturally occurs in low but very significant amounts in invertebrates, where it has hormonal roles, and in certain plant species, where it is believed to contribute to the deterrence of invertebrate predators. Studies in vivo and in vitro have revealed beneficial effects in mammals: anabolic, hypolipidemic, anti-diabetic, anti-inflammatory, hepatoprotective, etc. The possible mode of action in mammals has been determined recently, with the main mechanism involving the activation of the Mas1 receptor, a key component of the renin-angiotensin system, which would explain many of the pleiotropic effects observed in the different animal models. Processes have been developed to produce large amounts of pharmaceutical grade 20E, and regulatory preclinical studies have assessed its lack of toxicity. The effects of 20E have been evaluated in early stage clinical trials in healthy volunteers and in patients for the treatment of neuromuscular, cardio-metabolic or respiratory diseases. The prospects and limitations of developing 20E as a drug are discussed, including the requirement for a better evaluation of its safety and pharmacological profile and for developing a production process compliant with pharmaceutical standards.

23 citations

Journal ArticleDOI
TL;DR: In this article, the authors have used the aqueous extracts of Tinospora cordifolia (willd.) Hook in the form of Giloy Ghanvati, as a means of treatment to the SARS-CoV-2 spike-protein induced disease phenotype in a humanized zebrafish model.
Abstract: The current Severe Acute Respiratory Syndrome disease caused by Coronavirus-2 (SARS-CoV-2) has been a serious strain on the healthcare infrastructure mainly due to the lack of a reliable treatment option. Alternate therapies aimed at symptomatic relief are currently prescribed along with artificial ventilation to relieve distress. Traditional medicine in the form of Ayurveda has been used since ancient times as a holistic treatment option rather than targeted therapy. The practice of Ayurveda has several potent herbal alternatives for chronic cough, inflammation, and respiratory distress which are often seen in the SARS-CoV-2 infection. In this study we have used the aqueous extracts of Tinospora cordifolia (willd.) Hook. f. and Thomson in the form of Giloy Ghanvati, as a means of treatment to the SARS-CoV-2 spike-protein induced disease phenotype in a humanized zebrafish model. The introduction of spike-protein in the swim bladder transplanted with human lung epithelial cells (A549), caused an infiltration of pro-inflammatory immune cells such as granulocytes and macrophages into the swim bladder. There was also an increased systemic damage as exemplified by renal tissue damage and increased behavioral fever in the disease induction group. These features were reversed in the treatment group, fed with three different dosages of Giloy Ghanvati. The resultant changes in the disease phenotype were comparable to the group that were given the reference compound, Dexamethasone. These findings correlated well with various phyto-compounds detected in the Giloy Ghanvati and their reported roles in the viral disease phenotype amelioration.

22 citations