Abstract 4535: Inhibition of cell proliferation by (R,R')-4′-methoxy-1-naphthylfenoterol in breast cancer cell lines

Abstract

Abstract (R,R')-4′-methoxy-1-naphthylfenoterol (MNF) is a bitopic ligand that acts as an agonist of the β2-adrenergic receptor and an antagonist of the orphan G-protein-coupled receptor GPR55. Activation of GPR55 is pro-oncogenic through cannabinoid-related signal transduction and MNF treatment inhibits proliferation of different tumor cell lines, representing cancers of the liver, pancreas and brain. Of significance, MNF exerts antitumor activity in a xenograft glioma model in nude mice. In the current study, the anti-proliferative response mediated by MNF has been examined in human breast cancer cell lines. In this study, MCF-7 and MDA-MB-231 cells were screened for the presence of epidermal growth factor receptor (EGFR) and GPR55 proteins by Western blotting. The EGFR in such cancer cells plays a key role in the control of growth and proliferation. When compared to MCF-7 cells, MDA-MB-231 cells contained high levels of EGFR and GPR55 and showed exquisite sensitivity to MNF as evidenced by the significant reduction in constitutive phosphorylation of the extracellular signal-regulated kinase (ERK1/2), with an IC50 of 0.08 nM. [3H]-Thymidine incorporation assay was performed and revealed that MNF elicited a 2-fold higher growth inhibition in MDA-MB-231 cells as compared to MCF-7 cells (50% vs. 24.9% inhibition at 10 µM of MNF; p<0.001). Evidence for the altered expression and/or signaling pathway activation triggered by EGFR and GPR55 in response to MNF will be presented. We conclude that MDA-MB-231 cells represent a suitable model for the study of possible crosstalk between two classes of pro-oncogenic cell surface receptors and the analysis of MNF as novel therapeutic agent for the management of cancer. This work was supported entirely by the Intramural Research Program of the National Institute on Aging, NIH. Citation Format: Rajib K. Paul, Artur Wnorowski, Michel Bernier, Irving W. Wainer. Inhibition of cell proliferation by (R,R')-4′-methoxy-1-naphthylfenoterol in breast cancer cell lines. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4535. doi:10.1158/1538-7445.AM2014-4535