User menu

Accès à distance ? S'identifier sur le proxy UCLouvain

AM404 and VDM 11 non-specifically inhibit C6 glioma cell proliferation at concentrations used to block the cellular accumulation of the endocannabinoid anandamide

Primary tabs

Jonsson, Kent-Olov Andersson, Anna Jacobsson, Stig O.P. Vandevoorde, Séverine [UCL] Lambert, Didier [UCL] Fowler, Christopher J.

AM404 [N-(4-hydroxyphenyl)arachidonylamide] and VDM 11 [(5Z,8Z,11Z,14Z)-N-(4-hydroxy-2-methylphenyl)-5,8,11,14-eicosatetraenamide] are commonly used to prevent the cellular accumulation of the endocannabinoid anandamide, and thereby to potentiate its actions. However, it has been reported that AM404 can produce an influx of calcium into cells, which might be expected to have deleterious effects on cell proliferation. In the present study, AM404 and VDM 11 were found to reduce C6 glioma cell proliferation with IC50 values of 4.9 and 2.7 muM, respectively. The inhibition of cell proliferation following a 96-h exposure was not accompanied by dramatic caspase activation, and was not prevented by either a combination of cannabinoid and vanilloid receptor antagonists, or by the antioxidant alpha-tocopherol, suggestive of a non-specific mode of action. Similar results were seen with palmitoylisopropylamide, although this compound only produced significant inhibition of cell proliferation at 30 muM concentrations. AM404 (1 muM), VDM 11 (1 muM) and palmitoylisopropylamide (3-30 muM), i.e. concentrations producing relatively modest effects on cell proliferation per se, reduced the vanilloid receptor-mediated antiproliferative effects of anandamide, as would be expected for compounds preventing the cellular accumulation of anandamide (and thereby access to its binding site on the vanilloid receptor). It is concluded that concentrations of AM404 and VDM 11 that are generally used to reduce the cellular accumulation of anandamide have deleterious effects upon cell proliferation, and that lower concentrations of these compounds may be more appropriate to use in vitro.

Document type Article de périodique (Journal article) – Article de recherche
Access type Accès restreint
Publication date 2003
Language Anglais
Journal information "Archives of Toxicology" - Vol. 77, no. 4, p. 201-207 (2003)
Peer reviewed yes
Publisher Springer (Heidelberg)
issn 0340-5761
e-issn 1432-0738
Publication status Publié
Affiliation UCL - MD/FARM - Ecole de pharmacie
Keywords Anandamide ; Uptake inhibitors ; Cannabinoid receptors ; Vanilloid receptors ; Cell proliferation ; Glioma cells
Links
  1. Baker D, Pryce G, Croxford JL, Brown P, Pertwee RG, Makriyannis A, Khanolkar A, Layward L, Fezza F, Bisogno T, Di Marzo, V (2001) Endocannabinoids control spasticity in a multiple sclerosis model. FASEB J 15:300–302
  2. Beltramo M., Functional Role of High-Affinity Anandamide Transport, as Revealed by Selective Inhibition, 10.1126/science.277.5329.1094
  3. Chen Wei-Chung, Huang Jong-Khing, Cheng Jin-Shiung, Tsai Jack Chaur-Ren, Chiang An-Jen, Chou Kang-Ju, Liu Chun-Peng, Jan Chung-Ren, AM-404 elevates renal intracellular Ca2+, questioning its selectivity as a pharmacological tool for investigating the anandamide transporter, 10.1016/s1056-8719(01)00148-4
  4. De Petrocellis Luciano, Bisogno Tiziana, Davis John B, Pertwee Roger G, Di Marzo Vincenzo, Overlap between the ligand recognition properties of the anandamide transporter and the VR1 vanilloid receptor: inhibitors of anandamide uptake with negligible capsaicin-like activity, 10.1016/s0014-5793(00)02082-2
  5. De Petrocellis Luciano, Bisogno Tiziana, Maccarrone Mauro, Davis John B., Finazzi-Agrò Alessandro, Di Marzo Vincenzo, The Activity of Anandamide at Vanilloid VR1 Receptors Requires Facilitated Transport across the Cell Membrane and Is Limited by Intracellular Metabolism, 10.1074/jbc.m008555200
  6. Deutsch Dale G., Chin Suzette A., Enzymatic synthesis and degradation of anandamide, a cannabinoid receptor agonist, 10.1016/0006-2952(93)90486-g
  7. Deutsch Dale G., Glaser Sherrye T., Howell Judy M., Kunz Jeffrey S., Puffenbarger Robyn A., Hillard Cecilia J., Abumrad Nada, The Cellular Uptake of Anandamide Is Coupled to Its Breakdown by Fatty-acid Amide Hydrolase, 10.1074/jbc.m003161200
  8. Fowler C.J., Jacobsson S.O.P., Cellular transport of anandamide, 2-arachidonoylglycerol and palmitoylethanolamide—targets for drug development?, 10.1054/plef.2001.0357
  9. Fowler CJ, Jonsson K-O, Tiger G (2001) Fatty acid amide hydrolase: biochemistry, pharmacology, and therapeutic possibilities for an enzyme hydrolyzing anandamide, 2-arachidonoylglycerol, palmitoylethanolamide, and oleamide. Biochem Pharmacol 62; 517–526
  10. Fowler CJ, Jonsson KO, Andersson AS, Jacobsson SOP (2002) Non-specific effects of anandamide uptake inhibitors upon C6 glioma cell proliferation. In: 2002 Abstract Viewer/Itinerary Planner: Society for Neuroscience, Washington DC. Program No. 730.7. Available online http://sfn.scholarone.com/itin2002
  11. Glaser ST, Studholme KM, Fatade F, Yazulla S, Abumrad N, Deutsch DG (2002) Is there an anandamide transporter? In: Program of 2002 Symposium on the Cannabinoids, International Cannabinoid Research Society, Burlington VT, Abstract 9
  12. Högestätt E.D., Zygmunt P.M., Cardiovascular pharmacology of anandamide, 10.1054/plef.2001.0346
  13. Jacobsson Stig O P, Fowler Christopher J, Characterization of palmitoylethanolamide transport in mouse Neuro-2a neuroblastoma and rat RBL-2H3 basophilic leukaemia cells: comparison with anandamide, 10.1038/sj.bjp.0704029
  14. Jacobsson SOP, Wallin T, Fowler CJ (2001) Inhibition of rat C6 glioma cell proliferation by endogenous and synthetic cannabinoids. Relative involvement of cannabinoid and vanilloid receptors. J Pharmacol Exp Ther 299:951–959
  15. Jan Chung-Ren, Jiann Bang-Ping, Lu Yih-Chau, Chang Hong-Tai, Huang Jong-Khing, Effect of olvanil (N-vanillyl-cis-9-octadecenoamide) on cytosolic Ca2+ increase in renal tubular cells, 10.1016/s0024-3205(02)02174-4
  16. Jarrahian Abbas, Manna Sukumar, Edgemond William S., Campbell William B., Hillard Cecilia J., Structure-Activity Relationships Among N-Arachidonylethanolamine (Anandamide) Head Group Analogues for the Anandamide Transporter, 10.1046/j.1471-4159.2000.0742597.x
  17. Jonsson Kent-Olov, Vandevoorde Séverine, Lambert Didier M, Tiger Gunnar, Fowler Christopher J, Effects of homologues and analogues of palmitoylethanolamide upon the inactivation of the endocannabinoid anandamide, 10.1038/sj.bjp.0704199
  18. Jordt Sven-Eric, Julius David, Molecular Basis for Species-Specific Sensitivity to “Hot” Chili Peppers, 10.1016/s0092-8674(02)00637-2
  19. Kim M.-J., Jo D.-G., Hong G.-S., Kim B. J., Lai M., Cho D.-H., Kim K.-W., Bandyopadhyay A., Hong Y.-M., Kim D. H., Cho C., Liu J. O., Snyder S. H., Jung Y.-K., Calpain-dependent cleavage of cain/cabin1 activates calcineurin to mediate calcium-triggered cell death, 10.1073/pnas.152336999
  20. Lambert Didier M, DiPaolo Federica G, Sonveaux Pierre, Kanyonyo Martial, Govaerts Sophie J, Hermans Emmanuel, Bueb Jean-Luc, Delzenne Nathalie M, Tschirhart Eric J, Analogues and homologues of N-palmitoylethanolamide, a putative endogenous CB2 cannabinoid, as potential ligands for the cannabinoid receptors, 10.1016/s1388-1981(99)00132-8
  21. Lastres-Becker Isabel, Hansen Henrik H., Berrendero Fernando, De Miguel Rosario, Pérez-Rosado Alberto, Manzanares Jorge, Ramos José A., Fernández-Ruiz Javier, Alleviation of motor hyperactivity and neurochemical deficits by endocannabinoid uptake inhibition in a rat model of Huntington's disease : Cannabinoid Therapy in Huntington's Disease, 10.1002/syn.10054
  22. Maccarrone Mauro, Lorenzon Tatiana, Bari Monica, Melino Gerry, Finazzi-Agrò Alessandro, Anandamide Induces Apoptosis in Human Cells via Vanilloid Receptors : EVIDENCE FOR A PROTECTIVE ROLE OF CANNABINOID RECEPTORS, 10.1074/jbc.m005722200
  23. Mechoulam Raphael, Fride Ester, Di Marzo Vincenzo, Endocannabinoids, 10.1016/s0014-2999(98)00649-9
  24. Morita K, GLUCOCORTICOIDS ENHANCE SERUM DEPRIVATION- BUT NOT CALCIUM-INDUCED CYTOTOXICITY IN RAT C6 GLIOMA CELLS, 10.1006/cbir.1999.0494
  25. Patricelli Matthew P, Cravatt Benjamin F, Proteins regulating the biosynthesis and inactivation of neuromodulatory fatty acid amides, Vitamins & Hormones (2001) ISBN:9780127098623 p.95-131, 10.1016/s0083-6729(01)62002-8
  26. Piomelli D., Beltramo M., Glasnapp S., Lin S. Y., Goutopoulos A., Xie X.-Q., Makriyannis A., Structural determinants for recognition and translocation by the anandamide transporter, 10.1073/pnas.96.10.5802
  27. Rakhshan F, Day TA, Blakely RD, Barker EL (2000) Carrier-mediated uptake of the endogenous cannabinoid anandamide in RBL-2H3 cells. J Pharmacol Exp Ther 292:960–967
  28. Ray Swapan K, Wilford Gloria G, Crosby Chris V, Hogan Edward L, Banik Naren L, Diverse stimuli induce calpain overexpression and apoptosis in C6 glioma cells, 10.1016/s0006-8993(99)01290-1
  29. Wernyj Roman P, Mattson Mark P, Christakos Sylvia, Expression of calbindin-D28k in C6 glial cells stabilizes intracellular calcium levels and protects against apoptosis induced by calcium ionophore and amyloid β-peptide, 10.1016/s0169-328x(98)00307-6
  30. Zygmunt Peter M, Chuang Huai-hu, Movahed Pouya, Julius David, Högestätt Edward D, The anandamide transport inhibitor AM404 activates vanilloid receptors, 10.1016/s0014-2999(00)00207-7
Bibliographic reference Jonsson, Kent-Olov ; Andersson, Anna ; Jacobsson, Stig O.P. ; Vandevoorde, Séverine ; Lambert, Didier ; et. al. AM404 and VDM 11 non-specifically inhibit C6 glioma cell proliferation at concentrations used to block the cellular accumulation of the endocannabinoid anandamide. In: Archives of Toxicology, Vol. 77, no. 4, p. 201-207 (2003)
Permanent URL http://hdl.handle.net/2078.1/41003