151 results on '"Vandier C"'
Search Results
2. Effect of Adenosine on CO2 Chemosensitivity : Functional, cellular and molecular studies
- Author
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Kumar, P., Conway, A. F., Vandier, C., Marshall, N. J., Bruynseels, J., Matthews, G. M., Back, Nathan, editor, Cohen, Irun R., editor, Kritchevsky, David, editor, Lajtha, Abel, editor, Paoletti, Rodolfo, editor, Lahiri, Sukhamay, editor, Prabhakar, Naduri R., editor, and Forster, Robert E., II, editor
- Published
- 2002
- Full Text
- View/download PDF
3. The SK3/KCa2.3 potassium channel is a new cellular target for edelfosine
- Author
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Potier, M, Chantome, A, Joulin, V, Girault, A, Roger, S, Besson, P, Jourdan, M-L, LeGuennec, J-Y, Bougnoux, P, and Vandier, C
- Published
- 2011
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- View/download PDF
4. Spontaneous transient outward currents and delayed rectifier K+ current: effects of hypoxia
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Vandier, C., Delpech, M., and Bonnet, P.
- Subjects
Hypoxia -- Physiological aspects ,Potassium channels -- Physiological aspects ,Calcium ions -- Physiological aspects ,Biological sciences - Abstract
A study was conducted to analyze the influence of hypoxia on spontaneous transient outward currents and delayed rectifier potassium channel current. Cells were placed in a 1-ml volume bath for electrophysiological recording.Results showed that the removal of external Ca2+ and thapsigargin eliminated the effects of hypoxia, indicating that hypoxia minimizes steady-state outward current by a Ca2+-dependent mechanism.
- Published
- 1998
5. Effect of Adenosine on CO2 Chemosensitivity
- Author
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Kumar, P., primary, Conway, A. F., additional, Vandier, C., additional, Marshall, N. J., additional, Bruynseels, J., additional, and Matthews, G. M., additional
- Published
- 2002
- Full Text
- View/download PDF
6. Hypoxia enhances agonist-induced pulmonary arterial contraction by increasing calcium sequestration
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Vandier, C., Delpech, M., Rebocho, M., and Bonnet, P.
- Subjects
Hypoxia -- Research ,Pulmonary artery -- Physiological aspects ,Calcium in the body -- Physiological aspects ,Noradrenaline -- Physiological aspects ,Biological sciences - Abstract
An experiment was performed to determine the effects of hypoxia on the rabbit's pulmonary artery through the administration of norepinephrine (NE). The additional purpose of the study was to assess the function of extracellular calcium during NE-induced contraction. Phasic and tonic contractions were observed in the intrapulmonary arterial rings. In conclusion, hypoxia increased the calcium pump activity of the pulmonary arterial rings and the concentration of calcium in the sarcoplasmic reticulum.
- Published
- 1997
7. Halothane differentially decreases 5-hydroxytryptamine-induced contractions in normal and chronic hypoxic rat pulmonary arteries
- Author
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De Crescenzo, V., Dubuis, E., Constantin, S., Rebocho, M., Girardin, C., Bonnet, P., and Vandier, C.
- Published
- 2001
8. Overexpression of certain transient receptor potential and Orai channels in prostate cancer is associated with decreased risk of systemic recurrence after radical prostatectomy
- Author
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Perrouin‐Verbe, M. A., primary, Schoentgen, N., additional, Talagas, M., additional, Garlantezec, R., additional, Uguen, A., additional, Doucet, L., additional, Rosec, S., additional, Marcorelles, P., additional, Potier‐Cartereau, M., additional, Vandier, C., additional, Ferec, C., additional, Fromont, G., additional, Fournier, G., additional, Valeri, A., additional, and Mignen, O., additional
- Published
- 2019
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- View/download PDF
9. PO-041 TNF pathway in metastatic colorectal cancer according to RAS status and implication of potassium channels
- Author
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Ibrahim, S., primary, Girault, A., additional, Babin, L., additional, Guéguinou, M., additional, Potier-Cartereau, M., additional, Vandier, C., additional, Paintaud, G., additional, Lecomte, T., additional, and Raoul, W., additional
- Published
- 2018
- Full Text
- View/download PDF
10. Glyco-phospho-glycero-ether lipid as modulator of SK3 ion channel and SK3-dependent cancer cell migration
- Author
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Sevrain, C. M., primary, Berthe, W., additional, Couthon-Gourvès, H., additional, Haelters, J. P., additional, Bouchet, A. M., additional, Chantôme, A., additional, Potier-Cartereau, M., additional, Vandier, C., additional, and Jaffrès, P. A., additional
- Published
- 2016
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11. P01 scorpion toxin, a potential therapeutic agent against glioblastoma
- Author
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Mlayah-Bellalouna, S., primary, Chantome, A., additional, Aissaoui, D., additional, Ben Aissa, R., additional, Chagour, T., additional, Vandier, C., additional, El Ayeb, M., additional, and Srairi-Abid, N., additional
- Published
- 2016
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12. Composés modulateur de l’activité du canal SK3 – action antimétastatique
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J.P., Haelters, Corbel, B., Simon, Gaëlle, Vandier, C., Potier, M., Joulin, V., Bougnoux, P., Chimie, Electrochimie Moléculaires et Chimie Analytique (CEMCA), Université de Brest (UBO)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Nutrition, croissance et cancer (U 1069) (N2C), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)
- Subjects
[CHIM]Chemical Sciences - Published
- 2010
13. Le canal calcique TRPV4 : une cible potentielle pour contrôler l’inflammation respiratoire
- Author
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Dalloneau, E., primary, Henry, C., additional, Brea, D., additional, Aimar, R., additional, Baranek, T., additional, Potier-Cartereau, M., additional, Esnard, F., additional, Vandier, C., additional, and Si-Tahar, M., additional
- Published
- 2014
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14. Ophiobolin A induces paraptosis-like cell death in human glioblastoma cells by decreasing BKCa channel activity.
- Author
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UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire, Bury, M, Girault, A, Mégalizzi, V, Spiegl-Kreinecker, S, Mathieu, V, Berger, W, Evidente, A, Kornienko, A, Gailly, Philippe, Vandier, C, Kiss, R, UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire, Bury, M, Girault, A, Mégalizzi, V, Spiegl-Kreinecker, S, Mathieu, V, Berger, W, Evidente, A, Kornienko, A, Gailly, Philippe, Vandier, C, and Kiss, R
- Abstract
Glioblastoma multiforme (GBM) is the most lethal and common malignant human brain tumor. The intrinsic resistance of highly invasive GBM cells to radiation- and chemotherapy-induced apoptosis accounts for the generally dismal treatment outcomes. This study investigated ophiobolin A (OP-A), a fungal metabolite from Bipolaris species, for its promising anticancer activity against human GBM cells exhibiting varying degrees of resistance to proapoptotic stimuli. We found that OP-A induced marked changes in the dynamic organization of the F-actin cytoskeleton, and inhibited the proliferation and migration of GBM cells, likely by inhibiting big conductance Ca(2+)-activated K(+) channel (BKCa) channel activity. Moreover, our results indicated that OP-A induced paraptosis-like cell death in GBM cells, which correlated with the vacuolization, possibly brought about by the swelling and fusion of mitochondria and/or the endoplasmic reticulum (ER). In addition, the OP-A-induced cell death did not involve the activation of caspases. We also showed that the expression of BKCa channels colocalized with these two organelles (mitochondria and ER) was affected in this programmed cell death pathway. Thus, this study reveals a novel mechanism of action associated with the anticancer effects of OP-A, which involves the induction of paraptosis through the disruption of internal potassium ion homeostasis. Our findings offer a promising therapeutic strategy to overcome the intrinsic resistance of GBM cells to proapoptotic stimuli.
- Published
- 2013
15. Voltage-gated sodium channels: New targets in cancer therapy?
- Author
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Université de Tours - Inserm U921 Nutrition, Croissanc eet Cancer, Gillet, L., Roger, S., Potier, M., Brisson, Lucie, Vandier, C., Besson, P., Le Guennec, J.-Y., Université de Tours - Inserm U921 Nutrition, Croissanc eet Cancer, Gillet, L., Roger, S., Potier, M., Brisson, Lucie, Vandier, C., Besson, P., and Le Guennec, J.-Y.
- Abstract
Early detection and treatment of cancers have increased survival and improved clinical outcome. The development of metastases is often associated with a poor prognostic of survival. Finding early markers of metastasis and developing new therapies against their development is a great challenge. Since a few years, there is more evidence that ion channels are involved in the oncogenic process. Among these, voltage-gated sodium channels expressed in non-nervous or non-muscular organs are often associated with the metastatic behaviour of different cancers. The aim of this review is to describe the current knowledge on the functional expression of voltage-gated sodium channels and their biological roles in different cancers such as prostate, breast, lung (small cells and non-small cells) and leukaemia. As a conclusion, we develop conceptual approaches to understand how such channels can be involved in the metastatic process and conclude that blockers targeted toward these channels are promising new therapeutic solutions against metastatic cancers. © 2010 Bentham Science Publishers.
- Published
- 2010
16. Episodic weakness due to mitochondrial DNA MT-ATP6/8 mutations
- Author
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Aure, K., primary, Dubourg, O., additional, Jardel, C., additional, Clarysse, L., additional, Sternberg, D., additional, Fournier, E., additional, Laforet, P., additional, Streichenberger, N., additional, Petiot, P., additional, Gervais-Bernard, H., additional, Vial, C., additional, Bedat-Millet, A.-L., additional, Drouin-Garraud, V., additional, Bouillaud, F., additional, Vandier, C., additional, Fontaine, B., additional, and Lombes, A., additional
- Published
- 2013
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- View/download PDF
17. Ophiobolin A induces paraptosis-like cell death in human glioblastoma cells by decreasing BKCa channel activity
- Author
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Bury, M, primary, Girault, A, additional, Mégalizzi, V, additional, Spiegl-Kreinecker, S, additional, Mathieu, V, additional, Berger, W, additional, Evidente, A, additional, Kornienko, A, additional, Gailly, P, additional, Vandier, C, additional, and Kiss, R, additional
- Published
- 2013
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18. Targeting SKCa Channels in Cancer: Potential New Therapeutic Approaches
- Author
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Girault, A., primary, Haelters, J.-P., additional, Potier-Cartereau, M., additional, Chantome, A., additional, Jaffres, P.-A., additional, Bougnoux, P., additional, Joulin, V., additional, and Vandier, C., additional
- Published
- 2012
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19. New Alkyl-Lipid Blockers of SK3 Channels Reduce Cancer Cell Migration and Occurrence of Metastasis
- Author
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Girault, A., primary, Haelters, J.-P., additional, Potier-Cartereau, M., additional, Chantome, A., additional, Pinault, M., additional, Marionneau-Lambot, S., additional, Oullier, T., additional, Simon, G., additional, Couthon-Gourves, H., additional, Jaffres, P.-A., additional, Corbel, B., additional, Bougnoux, P., additional, Joulin, V., additional, and Vandier, C., additional
- Published
- 2011
- Full Text
- View/download PDF
20. The SK3/KCa2.3 potassium channel is a new cellular target for edelfosine
- Author
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Potier, M, primary, Chantome, A, additional, Joulin, V, additional, Girault, A, additional, Roger, S, additional, Besson, P, additional, Jourdan, M‐L, additional, LeGuennec, J‐Y, additional, Bougnoux, P, additional, and Vandier, C, additional
- Published
- 2010
- Full Text
- View/download PDF
21. SK3 channel promotes melanoma cell migration
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Chantome, A., primary, Girault, A., additional, Potier, M., additional, Vaudin, P., additional, Collin, C., additional, Jourdan, M.L., additional, Pagès, J.C., additional, Bougnoux, P., additional, Vandier, C., additional, and Joulin, V., additional
- Published
- 2008
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22. 068 Modulation of hypotensive effects of bradykinin by cathepsin K
- Author
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Lecaille, F., primary, Vandier, C., additional, Godat, E., additional, Herve-Grepinet, V., additional, Brömme, D., additional, and Lalmanach, G., additional
- Published
- 2006
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23. Continuous inhalation of carbon monoxide attenuates hypoxic pulmonary hypertension development presumably through activation of BK channels
- Author
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DUBUIS, E, primary, POTIER, M, additional, WANG, R, additional, and VANDIER, C, additional
- Published
- 2005
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24. A Possible Dual Site of Action for Carbon Monoxide‐Mediated Chemoexcitation in the Rat Carotid Body
- Author
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Barbé, C., primary, Al‐Hashem, F., additional, Conway, A. F., additional, Dubuis, E., additional, Vandier, C., additional, and Kumar, P., additional
- Published
- 2002
- Full Text
- View/download PDF
25. Presynaptic action of adenosine on a 4‐aminopyridine‐sensitive current in the rat carotid body
- Author
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Vandier, C., primary, Conway, A. F., additional, Landauer, R. C., additional, and Kumar, P., additional
- Published
- 1999
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- View/download PDF
26. Hypoxia activates a potassium current in isolated smooth muscle cells from large pulmonary arteries of the rabbit
- Author
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Bonnet, P, primary, Vandier, C, additional, Cheliakine, C, additional, and Garnier, D, additional
- Published
- 1994
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27. Synergistic action of NS-004 and internal Ca^2^+ concentration in modulating pulmonary artery K^+ channels
- Author
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Vandier, C. and Bonnet, P.
- Published
- 1996
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28. Ophiobolin A induces paraptosis-like cell death in human glioblastoma cells by decreasing BKCa channel activity
- Author
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Antonio Evidente, Marina Bury, Christophe Vandier, Sabine Spiegl-Kreinecker, Mathieu, Alexander Kornienko, Alban Girault, Robert Kiss, Walter Berger, Mégalizzi, Philippe Gailly, Laboratoire de Toxicologie, Université libre de Bruxelles (ULB), Nutrition, croissance et cancer (U 1069) (N2C), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Department f Neurosurgery, Landesnervenklinik Wagner Jauregg Hospital in Linz, Department of Medicine I, Medical University Vienna, Dipartimento di Scienze Chimiche, Università degli studi di Napoli Federico II, Department of Chemistry and Biochemistry, Texas State University, laboratoire de Physiologie Cellulaire, Université Catholique de Louvain = Catholic University of Louvain (UCL), Vandier, Christophe, Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Naples Federico II = Università degli studi di Napoli Federico II, Bury, M., Girault, A., Megalizzi, V., Spiegl-Kreinecker, S., Mathieu, V., Berger, W., Evidente, A., Kornienko, A., Gailly, P., Vandier, C., and Kiss, R.
- Subjects
Cancer Research ,Patch-Clamp Techniques ,Patch-Clamp Technique ,Potassium ion homeostasis ,Endoplasmic Reticulum ,Paraptosis ,Membrane Potentials ,Antineoplastic Agent ,0302 clinical medicine ,Cell Movement ,Homeostasis ,Large-Conductance Calcium-Activated Potassium Channel alpha Subunits ,Caspase ,0303 health sciences ,biology ,Cell Death ,Brain Neoplasms ,Ophiobolin A ,3. Good health ,Cell biology ,Mitochondria ,030220 oncology & carcinogenesis ,Original Article ,Human ,ophiobolin A ,Programmed cell death ,Sesterterpenes ,BKCa channel ,Immunology ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Antineoplastic Agents ,Paraptosi ,Membrane Potential ,Brain Neoplasm ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,Pharmacologie moléculaire et cellulaire ,[SDV.CAN] Life Sciences [q-bio]/Cancer ,Cell Line, Tumor ,Homeostasi ,Toxicologie pharmaceutique ,Humans ,Actin ,030304 developmental biology ,Cell Proliferation ,Sesterterpene ,Cell growth ,Endoplasmic reticulum ,glioblastoma ,Cell Biology ,Actins ,Cancérologie ,Apoptosis ,Cell culture ,Drug Resistance, Neoplasm ,Large-Conductance Calcium-Activated Potassium Channel alpha Subunit ,biology.protein ,Potassium ,paraptosis ,Glioblastoma - Abstract
Glioblastoma multiforme (GBM) is the most lethal and common malignant human brain tumor. The intrinsic resistance of highly invasive GBM cells to radiation- and chemotherapy-induced apoptosis accounts for the generally dismal treatment outcomes. This study investigated ophiobolin A (OP-A), a fungal metabolite from Bipolaris species, for its promising anticancer activity against human GBM cells exhibiting varying degrees of resistance to proapoptotic stimuli. We found that OP-A induced marked changes in the dynamic organization of the F-actin cytoskeleton, and inhibited the proliferation and migration of GBM cells, likely by inhibiting big conductance Ca(2+)-activated K(+) channel (BKCa) channel activity. Moreover, our results indicated that OP-A induced paraptosis-like cell death in GBM cells, which correlated with the vacuolization, possibly brought about by the swelling and fusion of mitochondria and/or the endoplasmic reticulum (ER). In addition, the OP-A-induced cell death did not involve the activation of caspases. We also showed that the expression of BKCa channels colocalized with these two organelles (mitochondria and ER) was affected in this programmed cell death pathway. Thus, this study reveals a novel mechanism of action associated with the anticancer effects of OP-A, which involves the induction of paraptosis through the disruption of internal potassium ion homeostasis. Our findings offer a promising therapeutic strategy to overcome the intrinsic resistance of GBM cells to proapoptotic stimuli., Journal Article, Research Support, Non-U.S. Gov't, SCOPUS: ar.j, info:eu-repo/semantics/published
- Published
- 2013
29. Spontaneous nanotube formation of an asymmetric glycolipid.
- Author
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Villanueva ME, Bar L, Redondo-Morata L, Namdar P, Ruysschaert JM, Pabst G, Vandier C, María Bouchet A, and Losada-Pérez P
- Abstract
Over the past decades, advances in lipid nanotechnology have shown that self-assembled lipid structures providing ease of preparation, chemical stability, and biocompatibility represent a landmark on the development of multidisciplinary technologies. Lipid nanotubes (LNTs) are a unique class of lipid self-assembled structures, bearing unique properties such as high-aspect ratio, tunable diameter size, and precise molecular recognition. They can be obtained either by the action of external factors to already formed vesicles or spontaneously, the latter depending strongly on subtle molecular features. Here, we report on the spontaneous formation of supported lipid nanotubes of a particular type of glycolipid, ohmline, whose hydrophobic core displays remarkable asymmetry. The combination of bulk and surface-sensitive techniques indicates that below its main transition, ohmline displays an interdigitated gel phase, likely driven by the unique asymmetry in its hydrophobic core. Enhanced order packing by interdigitation favors the formation of ohmline nanotubes in agreement with chiral-based models of nanotube formation. The findings presented in this work call for additional studies to link lipid molecular structure-assembly relationships, whose understanding is relevant for the controlled design of lipid nanotubes networks in particular and controlled design of soft-matter nanomaterials in general., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
30. Publisher Correction: LKB1-SIK2 loss drives uveal melanoma proliferation and hypersensitivity to SLC8A1 and ROS inhibition.
- Author
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Proteau S, Krossa I, Husser C, Guéguinou M, Sella F, Bille K, Irondelle M, Dalmasso M, Barouillet T, Cheli Y, Pisibon C, Arrighi N, Nahon-Estève S, Martel A, Gastaud L, Lassalle S, Mignen O, Brest P, Mazure NM, Bost F, Baillif S, Landreville S, Turcotte S, Hasson D, Carcamo S, Vandier C, Bernstein E, Yvan-Charvet L, Levesque MP, Ballotti R, Bertolotto C, and Strub T
- Published
- 2024
- Full Text
- View/download PDF
31. Endogenous ether lipids differentially promote tumor aggressiveness by regulating the SK3 channel.
- Author
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Papin M, Fontaine D, Goupille C, Figiel S, Domingo I, Pinault M, Guimaraes C, Guyon N, Cartron PF, Emond P, Lefevre A, Gueguinou M, Crottès D, Jaffrès PA, Ouldamer L, Maheo K, Fromont G, Potier-Cartereau M, Bougnoux P, Chantôme A, and Vandier C
- Subjects
- Humans, Cell Movement, MicroRNAs metabolism, MicroRNAs genetics, Lipids chemistry, Cell Line, Tumor, Neoplasm Invasiveness, Neoplasms metabolism, Neoplasms pathology, Neoplasms genetics, Small-Conductance Calcium-Activated Potassium Channels metabolism, Small-Conductance Calcium-Activated Potassium Channels genetics
- Abstract
SK3 channels are potassium channels found to promote tumor aggressiveness. We have previously demonstrated that SK3 is regulated by synthetic ether lipids, but the role of endogenous ether lipids is unknown. Here, we have studied the role of endogenous alkyl- and alkenyl-ether lipids on SK3 channels and on the biology of cancer cells. Experiments revealed that the suppression of alkylglycerone phosphate synthase or plasmanylethanolamine desaturase 1, which are key enzymes for alkyl- and alkenyl-ether-lipid synthesis, respectively, decreased SK3 expression by increasing micro RNA (miR)-499 and miR-208 expression, leading to a decrease in SK3-dependent calcium entry, cell migration, and matrix metalloproteinase 9-dependent cell adhesion and invasion. We identified several ether lipids that promoted SK3 expression and found a differential role of alkyl- and alkenyl-ether lipids on SK3 activity. The expressions of alkylglycerone phosphate synthase, SK3, and miR were associated in clinical samples emphasizing the clinical consistency of our observations. To our knowledge, this is the first report showing that ether lipids differentially control tumor aggressiveness by regulating an ion channel. This insight provides new possibilities for therapeutic interventions, offering clinicians an opportunity to manipulate ion channel dysfunction by adjusting the composition of ether lipids., Competing Interests: Conflict of interest The authors declare that they have no conflict of interests with the contents of article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
32. Enhanced macromolecular substance extravasation through the blood-brain barrier via acoustic bubble-cell interactions.
- Author
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Chen J, Escoffre JM, Romito O, Iazourene T, Presset A, Roy M, Potier Cartereau M, Vandier C, Wang Y, Wang G, Huang P, and Bouakaz A
- Subjects
- Brain metabolism, Acoustics, Microbubbles, Coloring Agents, Drug Delivery Systems methods, Cell Communication, Blood-Brain Barrier metabolism, Dextrans
- Abstract
The blood-brain barrier (BBB) maintains brain homeostasis, regulates influx and efflux transport, and provides protection to the brain tissue. Ultrasound (US) and microbubble (MB)-mediated blood-brain barrier opening is an effective and safe technique for drug delivery in-vitro and in-vivo. However, the exact mechanism underlying this technique is still not fully elucidated. The aim of the study is to explore the contribution of transcytosis in the BBB transient opening using an in-vitro model of BBB. Utilizing a diverse set of techniques, including Ca
2+ imaging, electron microscopy, and electrophysiological recordings, our results showed that the combined use of US and MBs triggers membrane deformation within the endothelial cell membrane, a phenomenon primarily observed in the US + MBs group. This deformation facilitates the vesicles transportation of 500 kDa fluorescent Dextran via dynamin-/caveolae-/clathrin- mediated transcytosis pathway. Simultaneously, we observed increase of cytosolic Ca2+ concentration, which is related with increased permeability of the 500 kDa fluorescent Dextran in-vitro. This was found to be associated with the Ca2+ -protein kinase C (PKC) signaling pathway. The insights provided by the acoustically-mediated interaction between the microbubbles and the cells delineate potential mechanisms for macromolecular substance permeability., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)- Published
- 2024
- Full Text
- View/download PDF
33. LKB1-SIK2 loss drives uveal melanoma proliferation and hypersensitivity to SLC8A1 and ROS inhibition.
- Author
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Proteau S, Krossa I, Husser C, Guéguinou M, Sella F, Bille K, Irondelle M, Dalmasso M, Barouillet T, Cheli Y, Pisibon C, Arrighi N, Nahon-Estève S, Martel A, Gastaud L, Lassalle S, Mignen O, Brest P, Mazure NM, Bost F, Baillif S, Landreville S, Turcotte S, Hasson D, Carcamo S, Vandier C, Bernstein E, Yvan-Charvet L, Levesque MP, Ballotti R, Bertolotto C, and Strub T
- Subjects
- Humans, Calcium, Cell Proliferation, Reactive Oxygen Species, Melanoma drug therapy, Uveal Neoplasms genetics, Uveal Neoplasms pathology
- Abstract
Metastatic uveal melanomas are highly resistant to all existing treatments. To address this critical issue, we performed a kinome-wide CRISPR-Cas9 knockout screen, which revealed the LKB1-SIK2 module in restraining uveal melanoma tumorigenesis. Functionally, LKB1 loss enhances proliferation and survival through SIK2 inhibition and upregulation of the sodium/calcium (Na
+ /Ca2+ ) exchanger SLC8A1. This signaling cascade promotes increased levels of intracellular calcium and mitochondrial reactive oxygen species, two hallmarks of cancer. We further demonstrate that combination of an SLC8A1 inhibitor and a mitochondria-targeted antioxidant promotes enhanced cell death efficacy in LKB1- and SIK2-negative uveal melanoma cells compared to control cells. Our study also identified an LKB1-loss gene signature for the survival prognostic of patients with uveal melanoma that may be also predictive of response to the therapy combination. Our data thus identify not only metabolic vulnerabilities but also new prognostic markers, thereby providing a therapeutic strategy for particular subtypes of metastatic uveal melanoma., (© 2023 The Authors. Published under the terms of the CC BY 4.0 license.)- Published
- 2023
- Full Text
- View/download PDF
34. Ether-lipids and cellular signaling: A differential role of alkyl- and alkenyl-ether-lipids?
- Author
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Papin M, Bouchet AM, Chantôme A, and Vandier C
- Subjects
- Plasmalogens metabolism, Ether, Ethers chemistry
- Abstract
Ether-lipids (EL) are specific lipids bearing a characteristic sn-1 ether bond. Depending on the ether or vinyl-ether nature of this bond, they are present as alkyl- or alkenyl-EL, respectively. Among EL, alkenyl-EL, also referred as plasmalogens in the literature, attract most of the scientific interest as they are the predominant EL species in eukaryotic cells, thus less is known about alkyl-EL. EL have been implicated in various signaling pathways and alterations in their quantity are frequently observed in pathologies such as neurodegenerative and cardiovascular diseases or cancer. However, it remains unknown whether both alkyl- and alkenyl-EL play the same roles in these processes. This review summarizes the roles and mechanisms of action of EL in cellular signaling and tries to discriminate between alkyl- and alkenyl-EL. We also focus on the involvement of EL-mediated alterations of cellular signaling in diseases and discuss the potential interest for EL in therapy., (Copyright © 2023 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.)
- Published
- 2023
- Full Text
- View/download PDF
35. Pivotal role of the ORAI3-STIM2 complex in the control of mitotic death and prostate cancer cell cycle progression.
- Author
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Kouba S, Buscaglia P, Guéguinou M, Ibrahim S, Félix R, Guibon R, Fromont G, Pigat N, Capiod T, Vandier C, Mignen O, and Potier-Cartereau M
- Abstract
Prostate cancer (PCa) represents one of the most frequent diagnosed cancer in males worldwide. Due to routine screening tests and the efficiency of available treatments, PCa-related deaths have significantly decreased over the past decades. However, PCa remains a critical threat if detected at a late stage in which, cancer cells would have already detached from the primary tumor to spread and invade other parts of the body. Calcium (Ca
2+ ) channels and their protein regulators are now considered as hallmarks of cancer and some of them have been well examined in PCa. Among these Ca2+ channels, isoform 3 of the ORAI channel family has been shown to regulate the proliferation of PCa cells via the Arachidonic Acid-mediated Ca2+ entry, requiring the involvement of STIM1 (Stromal Interaction Molecule 1). Still, no study has yet demonstrated a role of the "neglected" STIM2 isoform in PCa or if it may interact with ORAI3 to promote an oncogenic behavior. In this study, we demonstrate that ORAI3 and STIM2 are upregulated in human PCa tissues. In old KIMAP (Knock-In Mouse Prostate Adenocarcinoma) mice, ORAI3 and STIM2 mRNA levels were significantly higher than ORAI1 and STIM1. In vitro, we show that ORAI3-STIM2 interact under basal conditions in PC-3 cells. ORAI3 silencing increased Store Operated Ca2+ Entry (SOCE) and induced a significant increase of the cell population in G2/M phase of the cell cycle, consistent with the role of ORAI3 as a negative regulator of SOCE. Higher expression levels of CDK1-Y15/Cyclin B1 were detected and mitotic arrest-related death occurred after ORAI3 silencing, which resulted in activating Bax/Bcl-2-mediated apoptotic pathway and caspase-8 activation and cleavage. STIM2 and ORAI3 expression increased in M phase while STIM1 expression and SOCE amplitude significantly decreased. Taken together, ORAI3 -STIM2 complex allows a successful progression through mitosis of PCa cells by evading mitotic catastrophe., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)- Published
- 2023
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36. SK C a - and Kv1-type potassium channels and cancer: Promising therapeutic targets?
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Dupuy M, Gueguinou M, Potier-Cartereau M, Lézot F, Papin M, Chantôme A, Rédini F, Vandier C, and Verrecchia F
- Subjects
- Humans, Apoptosis, Ion Channels, Potassium Channels, Shaker Superfamily of Potassium Channels, Neoplasms pathology
- Abstract
Ion channels are transmembrane structures that allow the passage of ions across cell membranes such as the plasma membrane or the membranes of various organelles like the nucleus, endoplasmic reticulum, Golgi apparatus or mitochondria. Aberrant expression of various ion channels has been demonstrated in several tumor cells, leading to the promotion of key functions in tumor development, such as cell proliferation, resistance to apoptosis, angiogenesis, invasion and metastasis. The link between ion channels and these key biological functions that promote tumor development has led to the classification of cancers as oncochannelopathies. Among all ion channels, the most varied and numerous, forming the largest family, are the potassium channels, with over 70 genes encoding them in humans. In this context, this review will provide a non-exhaustive overview of the role of plasma membrane potassium channels in cancer, describing 1) the nomenclature and structure of potassium channels, 2) the role of these channels in the control of biological functions that promotes tumor development such as proliferation, migration and cell death, and 3) the role of two particular classes of potassium channels, the SKCa- and Kv1- type potassium channels in cancer progression., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)
- Published
- 2023
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37. Insights into the mechanisms governing P01 scorpion toxin effect against U87 glioblastoma cells oncogenesis.
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Mlayah-Bellalouna S, Aissaoui-Zid D, Chantome A, Jebali J, Souid S, Ayedi E, Mejdoub H, Belghazi M, Marrakchi N, Essafi-Benkhadir K, Vandier C, and Srairi-Abid N
- Abstract
The emerging concept of small conductance Ca
2+ -activated potassium channels (SKCa ) as pharmacological target for cancer treatment has significantly increased in recent years. In this study, we isolated the P01 toxin from Androctonus australis (Aa) scorpion venom and investigated its effect on biological properties of glioblastoma U87, breast MDA-MB231 and colon adenocarcinoma LS174 cancer cell lines. Our results showed that P01 was active only on U87 glioblastoma cells. It inhibited their proliferation, adhesion and migration with IC50 values in the micromolar range. We have also shown that P01 reduced the amplitude of the currents recorded in HEK293 cells expressing SK2 channels with an IC50 value of 3 pM, while it had no effect on those expressing SK3 channels. The investigation of the SKCa channels expression pattern showed that SK2 transcripts were expressed differently in the three cancer cell lines. Particularly, we highlighted the presence of SK2 isoforms in U87 cells, which could explain and rely on the specific activity of P01 on this cell line. These experimental data highlighted the usefulness of scorpion peptides to decipher the role of SKCa channels in the tumorigenesis process, and develop potential therapeutic molecules targeting glioblastoma with high selectivity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Mlayah-Bellalouna, Aissaoui-Zid, Chantome, Jebali, Souid, Ayedi, Mejdoub, Belghazi, Marrakchi, Essafi-Benkhadir, Vandier and Srairi-Abid.)- Published
- 2023
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38. Orai1/KCa/SigmaR1 complex, the cancer cell suicide squad.
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Gautier M and Vandier C
- Subjects
- Humans, Calcium metabolism, Cell Line, Tumor, ORAI1 Protein, Stromal Interaction Molecule 1, Neoplasms
- Published
- 2022
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39. The Sodium-Calcium Exchanger Controls the Membrane Potential of AFT024: A Mesenchymal Stem Cell Hematopoietic Niche Forming Line.
- Author
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Potier-Cartereau M, Gautier M, Ravalet N, Ducrocq E, Hamard S, LeGuennec JY, Vandier C, and Herault O
- Abstract
The aim of this study was to characterize the functional expression of sodium-calcium exchangers on AFT024 cell line, a murine model of mesenchymal stem/stromal cells (MSCs) supporting human primitive hematopoiesis. All current-clamp and voltage-clamp experiments were performed using the perforated patch whole-cell recording technique with amphotericin B. The membrane potential of -14 mV shifted to -35 mV when lowering the external sodium concentration to 0.33 mM and an increase of cytosolic calcium concentration was observed. KB-R7943, a selective blocker of cardiac sodium-calcium exchangers, also named NCX1 , induced a hyperpolarization at physiological sodium concentration while it blocked the hyperpolarization observed at low sodium concentration. This demonstrates for the first time the presence of the sodium-calcium exchangers in AFT024 cells and provides initial evidence that the membrane potential of these stromal cells is maintained depolarized by this exchanger. Lowering external sodium concentration and KB-R7943 had no effect on the membrane potential of 2018 cells, a nonhematopoietic-supportive cell line. Since NCX1 is differentially expressed in AFT024 cells as compared with nonhematopoietic supportive cells with more restricted differentiation potential, this study suggests a potential role of this sodium-calcium exchanger, in the differentiation process or hematopoietic support of MSCs., (Copyright 2022, Mary Ann Liebert, Inc., publishers.)
- Published
- 2022
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40. Bioelectricity of the Tumor Microenvironment.
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Buchanan PJ and Vandier C
- Published
- 2022
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41. Curcumin and NCLX inhibitors share anti-tumoral mechanisms in microsatellite-instability-driven colorectal cancer.
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Guéguinou M, Ibrahim S, Bourgeais J, Robert A, Pathak T, Zhang X, Crottès D, Dupuy J, Ternant D, Monbet V, Guibon R, Flores-Romero H, Lefèvre A, Lerondel S, Le Pape A, Dumas JF, Frank PG, Girault A, Chautard R, Guéraud F, García-Sáez AJ, Ouaissi M, Emond P, Sire O, Hérault O, Fromont-Hankard G, Vandier C, Tougeron D, Trebak M, Raoul W, and Lecomte T
- Subjects
- Animals, Calcium metabolism, Calcium Signaling, Humans, Mice, Microsatellite Repeats, Mitochondrial Proteins metabolism, Colorectal Neoplasms drug therapy, Colorectal Neoplasms genetics, Curcumin pharmacology, Microsatellite Instability, Sodium-Calcium Exchanger antagonists & inhibitors
- Abstract
Background and Aims: Recent evidences highlight a role of the mitochondria calcium homeostasis in the development of colorectal cancer (CRC). To overcome treatment resistance, we aimed to evaluate the role of the mitochondrial sodium-calcium-lithium exchanger (NCLX) and its targeting in CRC. We also identified curcumin as a new inhibitor of NCLX., Methods: We examined whether curcumin and pharmacological compounds induced the inhibition of NCLX-mediated mitochondrial calcium (mtCa
2+ ) extrusion, the role of redox metabolism in this process. We evaluated their anti-tumorigenic activity in vitro and in a xenograft mouse model. We analyzed NCLX expression and associations with survival in The Cancer Genome Atlas (TCGA) dataset and in tissue microarrays from 381 patients with microsatellite instability (MSI)-driven CRC., Results: In vitro, curcumin exerted strong anti-tumoral activity through its action on NCLX with mtCa2+ and reactive oxygen species overload associated with a mitochondrial membrane depolarization, leading to reduced ATP production and apoptosis. NCLX inhibition with pharmacological and molecular approaches reproduced the effects of curcumin. NCLX inhibitors decreased CRC tumor growth in vivo. Both transcriptomic analysis of TCGA dataset and immunohistochemical analysis of tissue microarrays demonstrated that higher NCLX expression was associated with MSI status, and for the first time, NCLX expression was significantly associated with recurrence-free survival., Conclusions: Our findings highlight a novel anti-tumoral mechanism of curcumin through its action on NCLX and mitochondria calcium overload that could benefit for therapeutic schedule of patients with MSI CRC., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)- Published
- 2022
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42. CaV1.3 enhanced store operated calcium promotes resistance to androgen deprivation in prostate cancer.
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O'Reilly D, Downing T, Kouba S, Potier-Cartereau M, McKenna DJ, Vandier C, and Buchanan PJ
- Subjects
- Androgen Antagonists pharmacology, Androgen Antagonists therapeutic use, Androgens pharmacology, Androgens therapeutic use, Animals, Calcium metabolism, Cell Line, Tumor, Humans, Male, Mice, Up-Regulation, Prostatic Neoplasms drug therapy, Prostatic Neoplasms metabolism, Prostatic Neoplasms, Castration-Resistant drug therapy, Prostatic Neoplasms, Castration-Resistant genetics, Prostatic Neoplasms, Castration-Resistant metabolism
- Abstract
Androgen deprivation therapy (ADT) is the main treatment for advanced prostate cancer (PCa) but resistance results in progression to terminal castrate resistant PCa (CRPC), where there is an unmet therapeutic need. Aberrant intracellular calcium (Ca
i 2+ ) is known to promote neoplastic transformation and treatment resistance. There is growing evidence that voltage gated calcium channel (VGCC) expression is increased in cancer, particularly CACNA1D/CaV1.3 in CRPC. The aim of this study was to investigate if increased CaV1.3 drives resistance to ADT and determine its associated impact on Cai 2+ and cancer biology. Bioinformatic analysis revealed that CACNA1D gene expression is increased in ADT treated PCa patients. This was corroborated in both in vivo LNCaP xenograft mouse and in vitro PCa cell line models, which demonstrated a significant increase in CaV1.3 protein expression following ADT with bicalutamide. Expression was found to be of a shortened 170kDa CaV1.3 isoform associated with plasma and intracellular membranes, which failed to induce calcium influx following membrane depolarisation. Instead, under ADT CaV1.3 mediated a rise in basal cytosolic calcium and an increase in store operated calcium entry (SOCE). This mechanism was found to promote the proliferation and survival of ADT resistant CRPC cells. Overall, this study demonstrates for the first time in PCa that under ADT specific CaV1.3 isoforms promote an upregulation of SOCE which contributes to treatment resistance and CRPC biology. Thus, this novel oncochannel represents a target for therapeutic development to improve PCa patient outcomes., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)- Published
- 2022
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43. EGFR -Mutant Non-Small-Cell Lung Cancer at Surgical Stages: What Is the Place for Tyrosine Kinase Inhibitors?
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Cansouline X, Lipan B, Sizaret D, Tallet A, Vandier C, Carmier D, and Legras A
- Abstract
The ADAURA trial has been significant for the perception of EGFR tyrosine kinase inhibitors (TKIs) as a tool for early stage non-small-cell lung cancer (NSCLC). It produced such great insight that the main TKI, Osimertinib, was rapidly integrated into international guidelines for adjuvant use. However, EGFR -mutant NSCLC is a complex entity and has various targeting drugs, and the benefits for patients might not be as clear as they seem. We reviewed trials and meta-analyses considering TKI adjuvant and neoadjuvant use. We also explored the influence of mutation variability and financial evaluations. We found that TKIs often show disease-free survival (DFS) benefits, yet studies have struggled to improve the overall survival (OS); however, the results from the literature might be confusing because of variability in the stages and mutations. The safety profiles and adverse events are acceptable, but costs remain high and accessibility might not be optimal. TKIs are promising drugs that could allow for tailored treatment designs.
- Published
- 2022
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44. Development of a High-Performance Thin-Layer Chromatography Method for the Quantification of Alkyl Glycerolipids and Alkenyl Glycerolipids from Shark and Chimera Oils and Tissues.
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Papin M, Guimaraes C, Pierre-Aue B, Fontaine D, Pardessus J, Couthon H, Fromont G, Mahéo K, Chantôme A, Vandier C, and Pinault M
- Subjects
- Animals, Chromatography, Thin Layer, Ether, Ethers, Glycerol, Plant Oils, Fish Oils, Sharks, Lipids analysis
- Abstract
Ether lipids are composed of alkyl lipids with an ether bond at the sn-1 position of a glycerol backbone and alkenyl lipids, which possess a vinyl ether bond at the sn-1 position of the glycerol. These ether glycerolipids are present either as polar glycerophospholipids or neutral glycerolipids. Before studying the biological role of molecular species of ether glycerolipids, there is a need to separate and quantify total alkyl and alkenyl glycerolipids from biological samples in order to determine any variation depending on tissue or physiopathological conditions. Here, we detail the development of the first high-performance thin-layer chromatography method for the quantification of total alkyl and alkenyl glycerolipids thanks to the separation of their corresponding alkyl and alkenyl glycerols. This method starts with a reduction of all lipids after extraction, resulting in the reduction of neutral and polar ether glycerolipids into alkyl and alkenyl glycerols, followed by an appropriate purification and, finally, the linearly ascending development of alkyl and alkenyl glycerols on high-performance thin-layer chromatography plates, staining, carbonization and densitometric analysis. Calibration curves were obtained with commercial alkyl and alkenyl glycerol standards, enabling the quantification of alkyl and alkenyl glycerols in samples and thus directly obtaining the quantity of alkyl and alkenyl lipids present in the samples. Interestingly, we found a differential quantity of these lipids in shark liver oil compared to chimera. We quantified alkyl and alkenyl glycerolipids in periprostatic adipose tissues from human prostate cancer and showed the feasibility of this method in other biological matrices (muscle, tumor).
- Published
- 2022
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45. Data pertaining to aberrant intracellular calcium handling during androgen deprivation therapy in prostate cancer.
- Author
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O'Reilly D, Downing T, Kouba S, Potier-Cartereau M, McKenna DJ, Vandier C, and Buchanan P
- Abstract
The data generated here in relates to the research article "CaV1.3 enhanced store operated calcium promotes resistance to androgen deprivation in prostate cancer". A model of prostate cancer (PCa) progression to castration resistance was employed, with untreated androgen sensitive LNCaP cell line alongside two androgen deprived (bicalutamide) sublines, either 10 days (LNCaP-ADT) or 2 years (LNCaP-ABL) treatment, in addition to androgen insensitive PC3. With this PCa model, qPCR was used to examined fold change in markers linked to androgen resistance, androgen receptor ( AR ) and neuron specific enolase ( NSE ), observing an increase under androgen deprivation. In addition, the gene expression of a range of calcium channels was measured, with only the L-type Voltage gated calcium channel, CACNA1D , demonstrating an increase during androgen deprivation. With CACNA1D knockdown the channel was found not to influence the gene expression of calcium channels, ORAI1 and STIM1 . The calcium channel blocker (CCB), nifedipine, was employed to determine the impact of CaV1.3 on the observed store release and calcium entry measured via Fura-2AM ratiometric dye in our outlined PCa model. In both the presence and absence of androgen deprivation, nifedipine was found to have no impact on store release induced by thapsigargin (Tg) in 0mM Ca
2+ nor store operated calcium entry (SOCE) following the addition of 2mM Ca2+ . However, CACNA1D siRNA knockdown was able to reduce SOCE in PC3 cells. The effect of nifedipine on CaV1.3 in PCa biology was measured through cell proliferation assay, with no observed change in the presence of CCB. While siCACNA1D reduced PC3 cell proliferation. This data can be reused to inform new studies investigating altered calcium handling in androgen resistant prostate cancer. It provides insight into the mechanism of CaV1.3 and its functional properties in altered calcium in cancer, which can be of use to researchers investigating this channel in disease. Furthermore, it could be helpful in interpreting studies investigating CCB's as a therapeutic and in the development of future drugs targeting CaV1.3., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Author(s).)- Published
- 2022
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46. Strengthening Anti-Glioblastoma Effect by Multi-Branched Dendrimers Design of a Scorpion Venom Tetrapeptide.
- Author
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Moslah W, Aissaoui-Zid D, Aboudou S, Abdelkafi-Koubaa Z, Potier-Cartereau M, Lemettre A, ELBini-Dhouib I, Marrakchi N, Gigmes D, Vandier C, Luis J, Mabrouk K, and Srairi-Abid N
- Subjects
- Animals, Antineoplastic Agents chemistry, Cell Line, Tumor, Cell Proliferation drug effects, Dendrimers chemistry, Dendrimers pharmacology, Humans, Oligopeptides chemistry, Scorpion Venoms chemistry, Scorpions, Antineoplastic Agents pharmacology, Central Nervous System Neoplasms drug therapy, Glioblastoma drug therapy, Oligopeptides pharmacology, Scorpion Venoms pharmacology
- Abstract
Glioblastoma is the most aggressive and invasive form of central nervous system tumors due to the complexity of the intracellular mechanisms and molecular alterations involved in its progression. Unfortunately, current therapies are unable to stop its neoplastic development. In this context, we previously identified and characterized AaTs-1, a tetrapeptide (IWKS) from Androctonus autralis scorpion venom, which displayed an anti-proliferative effect against U87 cells with an IC
50 value of 0.57 mM. This peptide affects the MAPK pathway, enhancing the expression of p53 and altering the cytosolic calcium concentration balance, likely via FPRL-1 receptor modulation. In this work, we designed and synthesized new dendrimers multi-branched molecules based on the sequence of AaTs-1 and showed that the di-branched (AaTs-1-2B), tetra-branched (AaTs-1-4B) and octo-branched (AaTs-1-8B) dendrimers displayed 10- to 25-fold higher effects on the proliferation of U87 cells than AaTs-1. We also found that the effects of the newly designed molecules are mediated by the enhancement of the ERK1/2 and AKT phosphorylated forms and by the increase in p53 expression. Unlike AaTs-1, AaTs-1-8B and especially AaTs-1-4B affected the migration of the U87 cells. Thus, the multi-branched peptide synthesis strategy allowed us to make molecules more active than the linear peptide against the proliferation of U87 glioblastoma cells.- Published
- 2022
- Full Text
- View/download PDF
47. Potassium and Calcium Channel Complexes as Novel Targets for Cancer Research.
- Author
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Potier-Cartereau M, Raoul W, Weber G, Mahéo K, Rapetti-Mauss R, Gueguinou M, Buscaglia P, Goupille C, Le Goux N, Abdoul-Azize S, Lecomte T, Fromont G, Chantome A, Mignen O, Soriani O, and Vandier C
- Subjects
- Calcium metabolism, Calcium Channels metabolism, Humans, Lipids, Potassium metabolism, Potassium Channels metabolism, Neoplasms drug therapy, Potassium Channels, Voltage-Gated
- Abstract
The intracellular Ca
2+ concentration is mainly controlled by Ca2+ channels. These channels form complexes with K+ channels, which function to amplify Ca2+ flux. In cancer cells, voltage-gated/voltage-dependent Ca2+ channels and non-voltage-gated/voltage-independent Ca2+ channels have been reported to interact with K+ channels such as Ca2+ -activated K+ channels and voltage-gated K+ channels. These channels are activated by an increase in cytosolic Ca2+ concentration or by membrane depolarization, which induces membrane hyperpolarization, increasing the driving force for Ca2+ flux. These complexes, composed of K+ and Ca2+ channels, are regulated by several molecules including lipids (ether lipids and cholesterol), proteins (e.g. STIM), receptors (e.g. S1R/SIGMAR1), and peptides (e.g. LL-37) and can be targeted by monoclonal antibodies, making them novel targets for cancer research., (© 2020. Springer Nature Switzerland AG.)- Published
- 2022
- Full Text
- View/download PDF
48. AaTs-1: A Tetrapeptide from Androctonus australis Scorpion Venom, Inhibiting U87 Glioblastoma Cells Proliferation by p53 and FPRL-1 Up-Regulations.
- Author
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Aissaoui-Zid D, Saada MC, Moslah W, Potier-Cartereau M, Lemettre A, Othman H, Gaysinski M, Abdelkafi-Koubaa Z, Souid S, Marrakchi N, Vandier C, Essafi-Benkhadir K, and Srairi-Abid N
- Subjects
- Animals, Antineoplastic Agents chemistry, Humans, Oligopeptides chemistry, Scorpions, Antineoplastic Agents pharmacology, Cell Proliferation drug effects, Gene Expression Regulation, Neoplastic drug effects, Glioblastoma drug therapy, Glioblastoma metabolism, Oligopeptides pharmacology, Receptors, Formyl Peptide biosynthesis, Receptors, Lipoxin biosynthesis, Scorpion Venoms chemistry, Tumor Suppressor Protein p53 biosynthesis, Up-Regulation drug effects
- Abstract
Glioblastoma is an aggressive cancer, against which medical professionals are still quite helpless, due to its resistance to current treatments. Scorpion toxins have been proposed as a promising alternative for the development of effective targeted glioblastoma therapy and diagnostic. However, the exploitation of the long peptides could present disadvantages. In this work, we identified and synthetized AaTs-1, the first tetrapeptide from Androctonus australis scorpion venom (Aa), which exhibited an antiproliferative effect specifically against human glioblastoma cells. Both the native and synthetic AaTs-1 were endowed with the same inhibiting effect on the proliferation of U87 cells with an IC
50 of 0.56 mM. Interestingly, AaTs-1 was about two times more active than the anti-glioblastoma conventional chemotherapeutic drug, temozolomide (TMZ), and enhanced its efficacy on U87 cells. AaTs-1 showed a significant similarity with the synthetic peptide WKYMVm, an agonist of a G-coupled formyl-peptide receptor, FPRL-1, known to be involved in the proliferation of glioma cells. Interestingly, the tetrapeptide triggered the dephosphorylation of ERK, p38, and JNK kinases. It also enhanced the expression of p53 and FPRL-1, likely leading to the inhibition of the store operated calcium entry. Overall, our work uncovered AaTs-1 as a first natural potential FPRL-1 antagonist, which could be proposed as a promising target to develop new generation of innovative molecules used alone or in combination with TMZ to improve glioblastoma treatment response. Its chemical synthesis in non-limiting quantity represents a valuable advantage to design and develop low-cost active analogues to treat glioblastoma cancer.- Published
- 2021
- Full Text
- View/download PDF
49. Synthetic alkyl-ether-lipid promotes TRPV2 channel trafficking trough PI3K/Akt-girdin axis in cancer cells and increases mammary tumour volume.
- Author
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Guéguinou M, Felix R, Marionneau-Lambot S, Oullier T, Penna A, Kouba S, Gambade A, Fourbon Y, Ternant D, Arnoult C, Simon G, Bouchet AM, Chantôme A, Harnois T, Haelters JP, Jaffrès PA, Weber G, Bougnoux P, Carreaux F, Mignen O, Vandier C, and Potier-Cartereau M
- Abstract
The Transient Receptor Potential Vanilloid type 2 (TRPV2) channel is highly selective for Ca
2+ and can be activated by lipids, such as LysoPhosphatidylCholine (LPC). LPC analogues, such as the synthetic alkyl-ether-lipid edelfosine or the endogenous alkyl-ether-lipid Platelet Activating Factor (PAF), modulates ion channels in cancer cells. This opens the way to develop alkyl-ether-lipids for the modulation of TRPV2 in cancer. Here, we investigated the role of 2-Acetamido-2-Deoxy-l-O-Hexadecyl-rac-Glycero-3-PhosphatidylCholine (AD-HGPC), a new alkyl-ether-lipid (LPC analogue), on TRPV2 trafficking and its impact on Ca2+ -dependent cell migration. The effect of AD-HGPC on the TRPV2 channel and tumour process was further investigated using calcium imaging and an in vivo mouse model. Using molecular and pharmacological approaches, we dissected the mechanism implicated in alkyl-ether-lipids sensitive TRPV2 trafficking. We found that TRPV2 promotes constitutive Ca2+ entry, leading to migration of highly metastatic breast cancer cell lines through the PI3K/Akt-Girdin axis. AD-HGPC addresses the functional TRPV2 channel in the plasma membrane through Golgi stimulation and PI3K/Akt/Rac-dependent cytoskeletal reorganization, leading to constitutive Ca2+ entry and breast cancer cell migration (without affecting the development of metastasis), in a mouse model. We describe, for the first time, the biological role of a new alkyl-ether-lipid on TRPV2 channel trafficking in breast cancer cells and highlight the potential modulation of TRPV2 by alkyl-ether-lipids as a novel avenue for research in the treatment of metastatic cancer., (Copyright © 2021 Elsevier Ltd. All rights reserved.)- Published
- 2021
- Full Text
- View/download PDF
50. Zeb1 and SK3 Channel Are Up-Regulated in Castration-Resistant Prostate Cancer and Promote Neuroendocrine Differentiation.
- Author
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Bery F, Cancel M, Guéguinou M, Potier-Cartereau M, Vandier C, Chantôme A, Guibon R, Bruyère F, Fromont G, and Mahéo K
- Abstract
Therapeutic strategies for metastatic castration-resistant prostate cancer aim to target androgen receptor signaling. Despite initial survival benefits, treatment resistance invariably occurs, leading to lethal disease. Therapies targeting the androgen receptor can induce the emergence of a neuroendocrine phenotype and reactivate embryonic programs associated with epithelial to mesenchymal transition. We recently reported that dysregulation of the calcium signal can induce the transcription factor Zeb1, a key determinant of cell plasticity during tumor progression. The aim of this study was to determine whether the androgen receptor-targeted treatment Enzalutamide could induce dysregulation of the calcium signal involved in the progression toward epithelial to mesenchymal transition and neuroendocrine differentiation, contributing to therapeutic escape. Our results show that Zeb1 and the SK3 potassium channel are overexpressed in vivo in neuroendocrine castration-resistant prostate cancer and in vitro in LNCaP cells neurodifferentiated after Enzalutamide treatment. Moreover, the neuroendocrine phenotype is associated with a deregulation of the expression of Orai calcium channels. We showed that Zeb1 and SK3 are critical drivers of neuroendocrine differentiation. Interestingly, Ohmline, an SK3 inhibitor, can prevent the expression of Zeb1 and neuroendocrine markers induced by Enzalutamide. This study offers new perspectives to increase hormone therapy efficacy and improve clinical outcomes.
- Published
- 2021
- Full Text
- View/download PDF
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