Exosomes derived from embryonal and alveolar rhabdomyosarcoma carry differential miRNA cargo and promote invasion of recipient fibroblasts.

Rhabdomyosarcoma (RMS) is an aggressive childhood soft tissue tumor, which exists in oncoprotein PAX-FOXO1 fusion positive and fusion negative subtypes, with the fusion-positive RMS being characterized by a more aggressive clinical behavior. Exosomes are small membranous vesicles secreted into body fluids by multiple cell types, including tumor cells, and have been implicated in metastatic progression through paracrine signaling. We characterized exosomes secreted by a panel of 5 RMS cell lines. Expression array analysis showed that, for both fusion-positive and fusion-negative cells, exosome miRNA clustered well together and to a higher extent than cellular miRNA. While enriched miRNA in exosomes of fusion-negative RMS cells were distinct from those of fusion-positive RMS cells, the most significant predicted disease and functions in both groups were related to processes relevant to cancer and tissue remodelling. Functionally, we found that RMS-derived exosomes exerted a positive effect on cellular proliferation of recipient RMS cells and fibroblasts, induced cellular migration and invasion of fibroblasts, and promoted angiogenesis. These findings show that RMS-derived exosomes enhance invasive properties of recipient cells, and that exosome content of fusion-positive RMS is different than that of fusion-negative RMS, possibly contributing to the different metastatic propensity of the two subtypes.MPP grant from the American University of Beirut Medical Center, Faculty of Medicine and with support from the Lebanese University. Miss Ghina Rammal has PhD funding by Azm and Saade association. The Saab laboratory was also supported in part by the International Outreach Program at St Jude Children’s Research Hospital and the American Lebanese Syrian Associated Charities (ALSAC), Memphis, TN, and the Children’s Cancer Center of Lebanon in Beirut, Lebanon

Long-Term Exposure of Early-Transformed Human Mammary Cells to Low Doses of Benzo[a]pyrene and/or Bisphenol A Enhances Their Cancerous Phenotype via an AhR/GPR30 Interplay

It is of utmost importance to decipher the role of chronic exposure to low doses of environmental carcinogens on breast cancer progression. The early-transformed triple-negative human mammary MCF10AT1 cells were chronically (60 days) exposed to low doses (10−10 M) of Benzo[a]pyrene (B[a]P), a genotoxic agent, and/or Bisphenol A (BPA), an endocrine disruptor. Our study revealed that exposed MCF10AT1 cells developed, in a time-dependent manner, an acquired phenotype characterized by an increase in cancerous properties (anchorage independent growth and stem-like phenotype). Co-exposure of MCF10AT1 cells to B[a]P and BPA led to a significantly greater aggressive phenotype compared to B[a]P or BPA alone. This study provided new insights into the existence of a functional interplay between the aryl hydrocarbon receptor (AhR) and the G protein-coupled receptor 30 (GPR30) by which chronic and low-dose exposure of B[a]P and/or BPA fosters the progression of MCF10AT1 cells into a more aggressive substage. Experiments using AhR or GPR30 antagonists, siRNA strategies, and RNAseq analysis led us to propose a model in which AhR signaling plays a “driver role” in the AhR/GPR30 cross-talk in mediating long-term and low-dose exposure of B[a]P and/or BPA. Retrospective analysis of two independent breast cancer cohorts revealed that the AhR/GPR30 mRNA expression signature resulted in poor breast cancer prognosis, in particular in the ER-negative and the triple-negative subtypes. Finally, the study identified targeting AhR and/or GPR30 with specific antagonists as a strategy capable of inhibiting carcinogenesis associated with chronic exposure to low doses of B[a]P and BPA in MCF10AT1 cells. Altogether, our results indicate that the engagement of both AhR and GPR30 functions, in particular in an ER-negative/triple-negative context of breast cells, favors tumor progression and leads to poor prognosis. © Copyright © 2020 Donini, El Helou, Wierinckx, Győrffy, Aires, Escande, Croze, Clezardin, Lachuer, Diab-Assaf, Ghayad, Fervers, Cavaillès, Maguer-Satta and Cohen

<i>In vitro</i> antiproliferative activity of saffron extracts against human acute lymphoblastic T-cell human leukemia

16-21<span style="font-size:11.0pt;font-family: " times="" new="" roman","serif";mso-fareast-font-family:"times="" roman";mso-bidi-font-family:="" mangal;letter-spacing:-.1pt;mso-ansi-language:en-gb;mso-fareast-language:en-us;="" mso-bidi-language:hi"="" lang="EN-GB">Cancer is still considered as one of the most life threatening cause responsible for a huge number of annual deaths around the world. Particularly, leukemia is difficult to be cured. In this context, free radicals are one of the factors that cause or predispose to cancer. Hence, they should be controlled in the body by prophylactic or curative treatments. The aim of this study was to evaluate the antiproliferative effect against human acute lymphoblastic T-cell leukemia (Jurkat cell line) of the Lebanese saffron (Crocus sativus L.; Family Iridacea), and to detect which components of saffron are responsible for the growth inhibitor. Lebanese saffron decreased cell growth of Jurkat cells in a dose dependent manner. A mixture of crocin and safranal also decreased the number of Jurkat cells and the IC50 value of this mixture was lower than that of the whole saffron extract.</span

Prévention de la transition du cancer in situ vers un cancer invasif chez les femmes en surpoids/obèses : rôle des cellules myoépithéliales

International audienc

Identification de facteurs préventifs de la transition du CCIS (carcinome canalaire in situ) vers un CCI (carcinome canalaire invasif) chez les femmes en surpoids ou obèses

International audienc

In vitro evaluation of the biological activity of Lebanase medicinal plants extracts against herpes simplex virus type 1.

Medicinal plants extracts are interesting novel drugs for use as antimicrobial and antiviral agents. In this study we investigate the in vitro antiviral activity of eight ethanol medicinal plant extracts against Herpes simplex virus (HSV-1) infection on monkey kidney cells. Acyclovir, an antiviral agent currently applied for treatment of herpes virus type 1 infection, was used to compare the plant extracts therapeutic activity. The inhibitory concentrations (IC50) were determined for eight medicinal plants extracts obtained from the following plants: Calamintha origanifolia, Satureja thymbra, Prangos aspurela, Sidiritis Perfoliata, Aspurela glomerata, Erythreae Centaurium, Hyssopus officinalis and Salvia accetabulosa. Cytotoxicity was evaluated by MTT assay in Vero cells. The selective index (SI) of these medicinal plant extracts was used to prove the therapeutic activity. We found that C. origanifolia and S.thymbra extracts have the highest selective index (SI) in our data and are therefore potentially be used for treatment of HSV-1 disease

Novel methylsulfonyl chalcones as potential antiproliferative drugs for human prostate cancer: Involvement of the intrinsic pathway of apoptosis

International audienceLimited success has been achieved in extending the survival of patients with metastatic and hormone-refractory prostate cancer (HRPC). There is a strong need for novel agents in the treatment and prevention of HRPC. In the present study, the apoptotic mechanism of action of RG003 (2'-hydroxy-4- methylsulfonylchalcone) and RG005 (4'-chloro-2'-hydroxy-4- methylsulfonylchalcone) in association with intracellular signalling pathways was investigated in the hormone-independent prostate carcinoma cells PC-3 and DU145. We showed that these compounds induced apoptosis through the intrinsic pathway but not through the extrinsic one. We showed that synthetic chalcones induced an activation of caspase-9 but not caspase-8 in PC-3 cells. Even if both chalcones induced apoptosis in PC-3 cells, a dominant effect of RG003 treatment was observed resulting in a disruption of δm, caspase-9 and caspase-3 activation, PARP cleavage and DNA fragmentation. Furthermore, in regard to our results, it is clear that the simultaneous inhibition of Akt and NF-κB signalling can significantly contribute to the anticancer effects of RG003 and RG005 in PC-3 prostate cancer cells. NF-κB inhibition was correlated with the reduction of COX-2 expression and induction of apoptosis. Our results clearly indicate for the first time that RG003 and RG005 exert their potent anti proliferative and pro-apoptotic effects through the modulation of Akt/NF-κB/COX-2 signal transduction pathways in PC-3 prostate cancer cells with a dominant effect for RG00

Phytochemical and pharmacological properties of essential oils from Cedrus species

Natural products frequently exert pharmacological activities. The present review gives an overview of the ethnobotany, phytochemistry and pharmacology of the Cedrus genus, e.g. cytotoxic, spasmolytic immunomodulatory, antiallergic, anti-inflammatory and analgesic activities. Cancer patients frequently seek remedies from traditional medicinal plants that are believed to exert less side effects than conventional therapy with synthetic drugs. A long-lasting goal of anti-cancer and anti-microbial therapy research is to find compounds with reduced side effects compared to currently approved drugs. In this respect, Cedrus species might be of interest. The essential oil isolated from Cedrus libani leaves may bear potential for drug development due to its high concentrations of germacrene D and β-caryophyllene. The essential oils from Cedrus species also show bioactivity against bacteria and viruses. More preclinical analyses (e.g. in vivo experiments) as well as clinical trials are required to evaluate the potential of essential oils from Cedrus species for drug development