Abstract
(R,R')-4'-Methoxy-1-naphthylfenoterol (MNF) promotes growth inhibition and apoptosis of human HepG2 hepatocarcinoma cells via cannabinoid receptor (CBR) activation. The synthetic CB1R inverse agonist, AM251, has been shown to block the anti-mitogenic effect of MNF in these cells; however, AM251 is also an agonist of the recently deorphanized, lipid-sensing receptor, GPR55, whose upregulation contributes to carcinogenesis. Here, we investigated the role of MNF in GPR55 signaling in human HepG2 and PANC-1 cancer cell lines in culture by focusing first on internalization of the fluorescent ligand Tocrifluor 1117 (T1117). Initial results indicated that cell pretreatment with GPR55 agonists, including the atypical cannabinoid O-1602 and l-α-lysophosphatidylinositol, dose-dependently reduced the rate of cellular T1117 uptake, a process that was sensitive to MNF inhibition. GPR55 internalization and signaling mediated by O-1602 was blocked by MNF in GPR55-expressing HEK293 cells. Pretreatment of HepG2 and PANC-1 cells with MNF significantly abrogated the induction of ERK1/2 phosphorylation in response to AM251 and O-1602. Moreover, MNF exerted a coordinated negative regulation of AM251 and O-1602 inducible processes, including changes...Continue Reading
References
Apr 22, 1991·The American Journal of Cardiology·S Imai
Apr 1, 1980·Journal of Pharmacobio-dynamics·M Hachisu, T Koeda
Jan 1, 1995·Life Sciences·M Rinaldi-CarmonaG Le Fur
Mar 3, 1999·Journal of Medicinal Chemistry·R LanA Makriyannis
May 19, 2004·Biochemistry·Oliver HegenerHanns Häberlein
Aug 17, 2005·The Journal of Cell Biology·Diane S LidkeDonna J Arndt-Jovin
Aug 23, 2005·Molecular Pharmacology·Martin R PriceRuth A Ross
Sep 4, 2007·Biochemical and Biophysical Research Communications·Saori OkaTakayuki Sugiura
Oct 11, 2007·Proceedings of the National Academy of Sciences of the United States of America·James W WislerRobert J Lefkowitz
May 1, 2008·Journal of Cell Science·Markus Waldeck-WeiermairWolfgang F Graier
Feb 14, 2009·Endocrinology·Jennifer L FioriMichel Bernier
Mar 25, 2009·British Journal of Pharmacology·Graeme Milligan
May 26, 2009·FEBS Letters·Maciej PietrAna Juknat
Sep 3, 2009·The Journal of Biological Chemistry·Ankur KapurMary E Abood
Feb 9, 2010·British Journal of Pharmacology·C J DalyJ C McGrath
Feb 9, 2010·British Journal of Pharmacology·Christopher M HenstridgeAndrew J Irving
Mar 20, 2010·Pharmacology & Therapeutics·Haleli Sharir, Mary E Abood
Apr 8, 2010·Current Topics in Medicinal Chemistry·Tapio Nevalainen, Andrew J Irving
Jul 24, 2010·British Journal of Pharmacology·X ZhangJ E Groopman
Sep 8, 2010·Oncogene·C AndradasC Sánchez
Sep 15, 2010·Oncogene·R PiñeiroM Falasca
Mar 18, 2011·British Journal of Pharmacology·Josée Guindon, Andrea G Hohmann
Mar 23, 2011·Molecular Cell·Michelle C MendozaJohn Blenis
Apr 7, 2011·Cell Research·Nariman A B BalengaMaria Waldhoer
Sep 14, 2011·Annual Review of Pharmacology and Toxicology·Celine ValantArthur Christopoulos
Oct 27, 2011·The Journal of Biological Chemistry·Sharon Anavi-GofferRuth A Ross
Nov 1, 2011·Cancer Metastasis Reviews·Daniel J Hermanson, Lawrence J Marnett
Jan 31, 2012·Biochimica Et Biophysica Acta·Roberto Piñeiro, Marco Falasca
Apr 26, 2012·The Journal of Biological Chemistry·Lucía CallénPeter J McCormick
Jul 4, 2012·Oncogene·E Pérez-GómezC Sánchez
Sep 18, 2012·PloS One·Peng WuZhixiang Wang
Nov 20, 2012·The Journal of Biological Chemistry·Julia KarglMaria Waldhoer
Citations
Jun 27, 2014·Experimental Neurology·E Martínez-PinillaR Franco
Jan 21, 2016·Journal of Medicinal Chemistry·Paula MoralesNadine Jagerovic
Apr 19, 2015·Molecular Cancer·Dan HeChaojun Duan
Jul 18, 2016·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Nagendra S SinghIrving W Wainer
Dec 1, 2017·Acta Pharmacologica Sinica·Xiao-Lei ZhouWei Zou
Jun 20, 2019·Frontiers in Pharmacology·Paula Morales, Nadine Jagerovic
Apr 19, 2020·Molecular Biology Reports·George Zaki Ghali, Michael George Zaki Ghali
May 15, 2015·Anti-cancer Drugs·Sara CarpiPaola Nieri
Feb 16, 2017·Journal of Molecular Endocrinology·Eva TuduríRubén Nogueiras
Aug 1, 2018·Oncogene·R FerroM Falasca
Jul 1, 2017·Frontiers in Pharmacology·Maciej StrzemskiMagdalena Wójciak-Kosior
Feb 2, 2021·Experimental Dermatology·Koji SugawaraRalf Paus
Jul 28, 2021·Cancer Reports·Judah Glogauer, Jonathan Blay