Characterization of the antiproliferative activity of Xylopia aethiopica

Abstract Background Xylopia aethiopica, a plant found throughout West Africa, has both nutritional and medicinal uses. The present study aims to characterize the effects of extracts of this plant on cancer cells. Results We report that X. aethiopica extract prepared with 70% ethanol has antiproliferative activity against a panel of cancer cell lines. The IC50 was estimated at 12 μg/ml against HCT116 colon cancer cells, 7.5 μg/ml and &gt; 25 μg/ml against U937 and KG1a leukemia cells, respectively. Upon fractionation of the extract by HPLC, the active fraction induced DNA damage, cell cycle arrest in G1 phase and apoptotic cell death. By using NMR and mass spectrometry, we determined the structure of the active natural product in the HPLC fraction as ent-15-oxokaur-16-en-19-oic acid. Conclusion The main cytotoxic and DNA-damaging compound in ethanolic extracts of Xylopia aethiopica is ent-15-oxokaur-16-en-19-oic acid. </jats:sec

Up-regulation of cdc2 protein during paclitaxel-induced apoptosis

International audienceMicrotubule damages induced by paclitaxel inhibit proteasome-dependent degradation of cyclin B, resulting in a sustained activation of cyclin B/cdc2 kinase and a cell cycle arrest in mitosis. It has been previously shown that this kinase activity is also required for paclitaxel-induced apoptosis. We found here that paclitaxel increased cdc2 mRNA and protein levels and led to an accumulation of cdc2 in the active dephosphorylated form in NIH-OVCAR-3 cells. The addition of cycloheximide inhibited the paclitaxel-induced increase in cdc2 protein level, further indicating that paclitaxel stimulates cdc2 synthesis. This increase in cdc2 synthesis is a consequence of paclitaxel-induced arrest in mitosis. Indeed, dual analysis of DNA and cdc2 protein contents indicated that cdc2 up-regulation occurred in cells arrested with a G2/M DNA content. Furthermore, no up-regulation of cdc2 protein was observed when paclitaxel-treated cells were prevented from entering mitosis by treatment with purvalanol A, a cyclin-dependent kinase (CDK) inhibitor, or stimulated to exit mitosis with 2-AP, a non-specific kinase inhibitor. In addition, when paclitaxel-induced apoptosis was inhibited by Bcl-2 over-expression, cdc2 up-regulation did not occur, leading to a lower level of activation of the cyclin B/cdc2 complex. Taken together, these results indicated that paclitaxel-induced cdc2 protein synthesis participates in a positive feedback loop designed to increase the activity of cyclin B/cdc2 kinase and thus may play a role in paclitaxel-induced apoptosis

Characterization of the antiproliferative activity of Xylopia aethiopica

Abstract Background Xylopia aethiopica, a plant found throughout West Africa, has both nutritional and medicinal uses. The present study aims to characterize the effects of extracts of this plant on cancer cells. Results We report that X. aethiopica extract prepared with 70% ethanol has antiproliferative activity against a panel of cancer cell lines. The IC50 was estimated at 12 μg/ml against HCT116 colon cancer cells, 7.5 μg/ml and > 25 μg/ml against U937 and KG1a leukemia cells, respectively. Upon fractionation of the extract by HPLC, the active fraction induced DNA damage, cell cycle arrest in G1 phase and apoptotic cell death. By using NMR and mass spectrometry, we determined the structure of the active natural product in the HPLC fraction as ent-15-oxokaur-16-en-19-oic acid. Conclusion The main cytotoxic and DNA-damaging compound in ethanolic extracts of Xylopia aethiopica is ent-15-oxokaur-16-en-19-oic acid.</p

The Eucalyptus linker histone variant EgH1.3 cooperates with the transcription factor EgMYB1 to control lignin biosynthesis during wood formation

International audienceWood, also called secondary xylem, is a specialized vascular tissue constituted by different cell types that undergo a differentiation process involving deposition of thick, lignified secondary cell walls. The mechanisms needed to control the extent of lignin deposition depending on the cell type and the differentiation stage are far from being fully understood. We found that the Eucalyptus transcription factor EgMYB1, which is known to repress lignin biosynthesis, interacts specifically with a linker histone variant, EgH1.3. This interaction enhances the repression of EgMYB1' s target genes, strongly limiting the amount of lignin deposited in xylem cell walls. The expression profiles of EgMYB1 and EgH1.3 overlap in xylem cells at early stages of their differentiation as well as in mature parenchymatous xylem cells, which have no or only thin lignified secondary cell walls. This suggests that a complex between EgMYB1 and EgH1.3 integrates developmental signals to prevent premature or inappropriate lignification of secondary cell walls, providing a mechanism to fine-tune the differentiation of xylem cells in time and space. We also demonstrate a role for a linker histone variant in the regulation of a specific developmental process through interaction with a transcription factor, illustrating that plant linker histones have other functions beyond chromatin organization

The Eucalyptus transcription factor EgMYB1 interacts with the histone linker EgH1 to modulate woodformation.

International audienc

Rapport de Prospective du Conseil Scientifique de l’Institut des Sciences de l’Information et leurs Interactions (INS2I)

The production of a scientific prospective report corresponds to one of the missions of the Institutes Scientific Councils (CSI) of CNRS. Such a report is both for internal use by the CNRS (the head of the institution, institutes, national review committees) and for the scientific community at large. In this context the Scientific Council of the INS2I Institute of CNRS has decided to direct this prospective report around the positioning of information sciences and their interactions in the global scientific landscape. In this way, we wish to highlight the importance and role of our discipline in a period when our field is undergoing deep technological, societal and scientific evolutions.To bring this reflection to life, we have chosen to rely, among other things, on hearings of leading personalities from our domains. These hearings, conducted in small group sessions, gave rise to extremely rich discussions that fed the Board's thinking in preparing this report. They were conducted on the basis of a common framework structured around five themes:1.How to define our discipline? What are the major achievements?2.What are the possible evolutions in the next 10 to 20 years?3.What are the biggest challenges and risks?4.How will our discipline impact on other sciences? How to manage thematic mobility in research at the interfaces with other disciplines?5.How will our discipline impact society at large, particularly in terms of education and popular instruction?Finally, the forward-thinking carried out in this work is also informed by the work of the Board over the past four years, in particular with regard to the organization of thematic seminars. These seminars allowed us to reflect more specifically on about ten transversal or disciplinary themes. Many of the issues discussed during these seminars were also discussed through the preparatory stages for the preparation of this report, in particular around the place of women in our disciplines or even around ethical issues. The summaries of these seminars are given in the appendix to this document and the working documents are available for free access on the Council's website (https://csins2i.irisa.fr/).La rédaction d’un rapport de prospective scientifique correspond à une des missions des conseils scientifiques d’instituts (CSI) au CNRS. Un tel rapport est à la fois à usage interne au CNRS (directions d'établissement, d’instituts, comité national), et à destination de la communauté scientifique. Dans ce cadre et en concertation avec la direction de l’institut, le conseil scientifique de l’institut INS2I du CNRS a souhaité orienter ce rapport de prospective autour du positionnement des sciences de l’information et leurs interactions dans le paysage scientifique global. Nous souhaitons ainsi pointer l’importance et le rôle de notre discipline dans une période où notre domaine est traversé par de profondes évolutions technologiques, sociétales et scientifiques.Pour porter cette réflexion, nous avons fait le choix de nous appuyer, entre autres, sur des auditions de personnalités de nos domaines. Ces auditions, menées en petits groupes de discussion, ont donné lieu à des échanges extrêmement riches qui ont nourri la réflexion du conseil dans l'élaboration de ce rapport. Elles ont été conduites sur la base d’une trame commune articulée autour de cinq thèmes :1.Comment définir notre discipline ? Quelles en sont les grandes réalisations ?2.Quelles sont les évolutions envisageables dans les 10 à 20 prochaines années ?3.Quels sont les plus grands enjeux et risques ?4.Comment notre discipline va-t-elle impacter les autres sciences ? Comment gérer la mobilité thématique dans la recherche aux interfaces avec les autres disciplines ?5.Comment notre discipline va-t-elle impacter la société au sens large, concernant notamment l'enseignement et l'éducation populaire ?.Enfin, la prospective réalisée dans ce document se nourrit également du travail du conseil lors de ces quatre dernières années, en particulier autour de l’organisation de séminaires thématiques. Ces séminaires nous ont permis de porter une réflexion plus spécifique sur une dizaine de thèmes transversaux ou disciplinaires. Beaucoup des enjeux abordés lors de ces séminaires ont également été discutés à travers les ateliers préparatoires à l'élaboration de ce rapport, notamment autour de la place des femmes dans nos disciplines ou bien encore autour des enjeux d’éthique. Les synthèses de ces séminaires sont données en annexe de ce document et les documents de travail sont disponibles en accès libre sur le site internet du conseil (https://csins2i.irisa.fr/)

Rapport de Prospective du Conseil Scientifique de l’Institut des Sciences de l’Information et leurs Interactions (INS2I)

The production of a scientific prospective report corresponds to one of the missions of the Institutes Scientific Councils (CSI) of CNRS. Such a report is both for internal use by the CNRS (the head of the institution, institutes, national review committees) and for the scientific community at large. In this context the Scientific Council of the INS2I Institute of CNRS has decided to direct this prospective report around the positioning of information sciences and their interactions in the global scientific landscape. In this way, we wish to highlight the importance and role of our discipline in a period when our field is undergoing deep technological, societal and scientific evolutions.To bring this reflection to life, we have chosen to rely, among other things, on hearings of leading personalities from our domains. These hearings, conducted in small group sessions, gave rise to extremely rich discussions that fed the Board's thinking in preparing this report. They were conducted on the basis of a common framework structured around five themes:1.How to define our discipline? What are the major achievements?2.What are the possible evolutions in the next 10 to 20 years?3.What are the biggest challenges and risks?4.How will our discipline impact on other sciences? How to manage thematic mobility in research at the interfaces with other disciplines?5.How will our discipline impact society at large, particularly in terms of education and popular instruction?Finally, the forward-thinking carried out in this work is also informed by the work of the Board over the past four years, in particular with regard to the organization of thematic seminars. These seminars allowed us to reflect more specifically on about ten transversal or disciplinary themes. Many of the issues discussed during these seminars were also discussed through the preparatory stages for the preparation of this report, in particular around the place of women in our disciplines or even around ethical issues. The summaries of these seminars are given in the appendix to this document and the working documents are available for free access on the Council's website (https://csins2i.irisa.fr/).La rédaction d’un rapport de prospective scientifique correspond à une des missions des conseils scientifiques d’instituts (CSI) au CNRS. Un tel rapport est à la fois à usage interne au CNRS (directions d'établissement, d’instituts, comité national), et à destination de la communauté scientifique. Dans ce cadre et en concertation avec la direction de l’institut, le conseil scientifique de l’institut INS2I du CNRS a souhaité orienter ce rapport de prospective autour du positionnement des sciences de l’information et leurs interactions dans le paysage scientifique global. Nous souhaitons ainsi pointer l’importance et le rôle de notre discipline dans une période où notre domaine est traversé par de profondes évolutions technologiques, sociétales et scientifiques.Pour porter cette réflexion, nous avons fait le choix de nous appuyer, entre autres, sur des auditions de personnalités de nos domaines. Ces auditions, menées en petits groupes de discussion, ont donné lieu à des échanges extrêmement riches qui ont nourri la réflexion du conseil dans l'élaboration de ce rapport. Elles ont été conduites sur la base d’une trame commune articulée autour de cinq thèmes :1.Comment définir notre discipline ? Quelles en sont les grandes réalisations ?2.Quelles sont les évolutions envisageables dans les 10 à 20 prochaines années ?3.Quels sont les plus grands enjeux et risques ?4.Comment notre discipline va-t-elle impacter les autres sciences ? Comment gérer la mobilité thématique dans la recherche aux interfaces avec les autres disciplines ?5.Comment notre discipline va-t-elle impacter la société au sens large, concernant notamment l'enseignement et l'éducation populaire ?.Enfin, la prospective réalisée dans ce document se nourrit également du travail du conseil lors de ces quatre dernières années, en particulier autour de l’organisation de séminaires thématiques. Ces séminaires nous ont permis de porter une réflexion plus spécifique sur une dizaine de thèmes transversaux ou disciplinaires. Beaucoup des enjeux abordés lors de ces séminaires ont également été discutés à travers les ateliers préparatoires à l'élaboration de ce rapport, notamment autour de la place des femmes dans nos disciplines ou bien encore autour des enjeux d’éthique. Les synthèses de ces séminaires sont données en annexe de ce document et les documents de travail sont disponibles en accès libre sur le site internet du conseil (https://csins2i.irisa.fr/)