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

Impact du secrétome adipocytaire sur l’hormonothérapie dans le cancer du sein en situation de surpoids/obésité

National audienceL’obésité, facteur de risque établi de cancer du sein chez les femmes ménopausées, est aussi responsable de plus forts taux de récidives et de mortalité. Dans ce contexte, nos travaux évaluent l’impact du secrétome adipocytaire (SA) dans la moindre réponse à l’hormonothérapie. Pour cela, 1/ des cellules cancéreuses mammaires ont été soit co-cultivées avec des cellules souches adipeuses (CSAd) humaines (hMAD) différenciées en adipocytes matures (AM) soit cultivées en présence de milieux conditionnés (MC), puis traitées avec un anti-estrogène (anti-E ; Tamoxifène Tx ou Fulvestrant Fv). La prolifération cellulaire a été mesurée par fluorescence à la résazurine (Fluoroskan Ascent FL®, n=3) et suivie en temps réel par impédancemétrie (iCELLigence, n=3). 2/ L’impact du surpoids a été évalué en utilisant des AM différenciés à partir de CSAd de femmes minces ou obèses cultivées en présence de cellules MCF-7 et de Fv. Dans nos différents modèles, les SA sont capables de majorer la prolifération des cellules MCF-7, récepteur aux estrogènes positives (RE+), et d’inhiber totalement l’effet antiprolifératif du Tx et du Fv. L’utilisation de cellules MDA-MB-231 RE- a montré que le SA majore la prolifération cellulaire et contrecarre l’effet antiprolifératif du Tx, suggérant que les effets observés ne passeraient pas exclusivement par la voie du RE dans notre modèle. Par ailleurs, en utilisant des AM de femmes de poids variables, seuls les SA correspondant aux femmes d’IMC>30 amoindrissent l’efficacité du Fv, cet effet s’accompagnant d’une augmentation de l’expression du gène OB-R. Ainsi, nos résultats préliminaires suggèrent que le SA limiterait l’efficacité de l’hormonothérapie et ce, de façon plus prononcée en cas de surpoids, ce qui pourrait contribuer au processus d’échappement tumora

Bis(4-hydroxy-2H-chromen-2-one) Coumarin Induces Apoptosis in MCF-7 Human Breast Cancer Cells Through Aromatase Inhibition

AIM: The present investigation aimed to examine the therapeutic potential of the new coumarin derivative bis(4-hydroxy-2H-chromen-2-one) coumarin (4HC) against breast cancer. MATERIALS AND METHODS: For this purpose, the effects of 4HC treatment on the proliferation of MCF-7 breast cancer cells and on MCF-10a non-cancerous cells were evaluated using a fluorescent assay. Cell cycle distribution and apoptosis were measured by image cytometry. The expression level of aromatase (CYP19A1) and apoptosis-related genes were determined by real-time PCR. RESULTS: MCF-7 mammary cancer cell proliferation was significantly decreased within 24 h after treatment with 4HC at 50 muM, while no effect was observed on the viability of MCF-10a non-cancerous mammary cells. 4HC also increased the percentage of the cells in the G2/M phase, inducing apoptosis. Real-time PCR revealed that 4HC induced MCF-7 mortality through an up-regulation of Bax and a down-regulation of Bcl-2, resulting in an increase in caspase-3 gene expression. The increased expression of apoptosis-related genes was accompanied by a decrease in CYP19A1 gene expression. CONCLUSION: 4HC selectively inhibits proliferation of MCF-7cells in vitro. Moreover, 4HC has inhibitory effects on aromatase gene expression and promoting effects on apoptosis, in MCF-7 cells

Comparison of the anti-inflammatory and immunomodulatory mechanisms of two medicinal herbs: meadowsweet (Filipendula ulmaria) and harpagophytum (Harpagophytum procumbens).

International audienceBackground: Meadowsweet (Filipendula ulmaria) and Harpagophytum (H. procumbens) are two medicinal herbs traditionally used for their anti-inflammatory effect. Nonetheless, if the effects of the single compounds isolated from these plants have been well described, little is known about the molecular mechanisms behind whole extracts.Methods: We studied and compared the effects of methanolic extracts from the aerial parts of F. ulmaria (FUE) and from the roots of H. procumbens (HPE) on different markers of inflammation such as antioxidant capacity, leukocyte ROS production, COX-2/PGE2 pathway or cytokine secretions.Results: FUE proved to be better than HPE in terms of antioxidant capabilities. Even if their effect on COX-2/PGE2 were similar, we found that their immune-modulatory activities were quite different. In the basal state, the FUE favored cytokines associated with Th1 lymphocytes whereas the HPE decreased the secretion of IL-21 and IL-23, associated with Th17 cells. In PHA-stimulated cells, the HPE increased the characteristic cytokines of Th1 cells, whereas the effects of the FUE were more nuanced.Conclusion: Though both plants are known as anti-inflammatory herbs, these results suggested that, apart from their similar anti-inflammatory effect on COX-2/PGE2, both could improve neutrophil and monocyte recruitment, as well as monocytes/macrophages and Th1, and presumably Th17, activation. Therefore, their impact on immune response was more likely immunostimulant

In Vitro Anti-Inflammatory and Immunomodulatory Activities of an Extract from the Roots of Bupleurum rotundifolium

This article belongs to the Special Issue Biological Potential and Medical Use of Natural ExtractsInternational audienceBackground: Some Bupleurum species, such as the Bupleurum chinense DC. or the Bupleurum scorzonerifolium Willd have been extensively studied (especially their roots) for the treatment of inflammation. In contrast, only compounds extracted from the aerial parts of Bupleurum rotundifolium have been studied and showed anti-inflammatory or antiproliferative activities. This study was conducted to investigate the antioxidant, anti-inflammatory, and immunomodulatory effects of Bupleurum rotundifolium roots. Methods: To tackle the various aspects of inflammation, we studied in vitro a methanolic extract from the roots of Bupleurum rotundifolium on peripheral blood mononuclear cells (PBMCs), polymorphonuclear neutrophils (PMNs), and the monocytic cells THP-1. Its antioxidant capacities and iron-chelating activity were assessed. The extract was tested on THP-1 differentiation, reactive oxygen species (ROS) production by leukocytes, neutrophils chemotaxis, cytokines, PGE2 production, and NF-κB activation in PBMCs. Results: The extract showed a decreased ROS production in stimulated cells. It increased PBMC chemokine secretion and up-regulated the differentiation of THP-1 monocytes into macrophage-like cells, indicating a potential interest of the extract in the resolution of acute inflammation. In addition, the analysis of cytokine production suggests that Bupleurum rotundifolium has immunomodulatory properties. Conclusions: Cytokines secretion, especially IL-1β and IL-12p70, provided us with a set of indicators suggesting that the extract might be able to drive the polarization of macrophages and lymphocytes toward a Th2 anti-inflammatory profile in excessive inflammation