Abstract 1023: Regulation of cell proliferation by GPR55/cannabinoid receptors using (R,R’)-4’-methoxy-1-naphthylfenoterol in rat C6 glioma cell line.

Abstract

Abstract (R,R’)-4’-Methoxy-1-naphthylfenoterol (MNF) is a potent inhibitor of the proliferation of rat C6 glioma cells with an IC(50) of 0.45 nM and initial in vivo data indicate that the compound may be potentially useful in the treatment of malignant gliomas. MNF is an agonist of the β(2)-adrenergic receptor and an antagonist of the GPR55 receptor. Previous studies have demonstrated that MNF inhibits proliferation in 1321N1 astrocytoma cells via the β(2)-adrenergic receptor and in HepG2 hetapocallular carcinoma cells via GPR55. In this study, the mechanism of the observed MNF effect in C6 cells was investigated using [(3)H]-thymidine incorporation, cell motility assay, and internalization of the fluorescent GPR55 ligand, Tocrifluor 1117 (T1117). The anti-mitogenic response of MNF was not affected by the β(2)-AR antagonist 3-(isopropylamino)-1-[(7-methyl-4-indanyl)oxy]butan-2-ol (ICI 118,551). Cell treatment with synthetic agonists of cannabinoid receptors 1 and 2 (WIN-55212,2 and CP55940) led to growth inhibition, whereas pretreatment with AM251 (0.1-5 μM) dose-dependently blocked the anti-mitogenic responses of MNF. Both AM251 and the atypical cannabinoid O-1602 increased cell motility, which was blocked by MNF. Finally, there was marked inhibition in the cellular accumulation of T1117 in MNF-treated C6 glioma cells. These results indicate that MNF inhibits proliferation of C6 cells via GPR55/cannabinoid receptors and not via the β(2)-adrenergic receptor. This work was supported entirely by the Intramural Research Program of the NIA, NIH. Citation Format: Rajib K. Paul, Artur Wnorowski, Fred E. Indig, Michel Bernier, Irving W. Wainer. Regulation of cell proliferation by GPR55/cannabinoid receptors using (R,R’)-4’-methoxy-1-naphthylfenoterol in rat C6 glioma cell line. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1023. doi:10.1158/1538-7445.AM2013-1023