PANCREATIC CANCER & Cannabis studies
Overview
Science & Research
2013 - Study ~ Cannabinoids inhibit energetic metabolism and induce AMPK-dependent autophagy in pancreatic cancer cells.
2013 - Study ~ Comparative proteomic and phosphoproteomic profiling of pancreatic adenocarcinoma cells treated with CB1 or CB2 agonists.
2013 - Study ~ (R,R')-4'-Methoxy-1-naphthylfenoterol Targets GPR55-mediated Ligand Internalization and Impairs Cancer Cell Motility.
2011 - Study ~ Gemcitabine/cannabinoid combination triggers autophagy in pancreatic cancer cells through a ROS-mediated mechanism.2009 - Study ~ TRB3 links ER stress to autophagy in cannabinoid anti-tumoral action.
2008 - Study ~ Emerging role of cannabinoids in gastrointestinal and liver diseases: basic and clinical aspects.
2008 - Study ~ Cannabinoids in pancreatic cancer: Correlation with survival and pain.
2006 - Study - Cannabinoids Induce Apoptosis of Pancreatic Tumor Cells via Endoplasmic Reticulum Stress–Related Genes.
2006 - Study ~ Cannabinoid derivatives induce cell death in pancreatic MIA PaCa-2 cells via a receptor-independent mechanism.
2006 - News ~ Cannabinoids Halt Pancreatic Cancer, Breast Cancer Growth, Studies Say.
Recommended Cannabis Strains for Pancreatic Cancer
Cannabinoids Induce Apoptosis of Pancreatic Tumor Cells via Endoplasmic Reticulum Stress–Related Genes
Endocrinology, doi:10.1210/en.141.1.118
Endocrinology Vol. 141, No. 1 118-126
Copyright © 2000 by The Endocrine Society
Istituto per la Chimica di Molecole di Interesse Biologico (D.M., T.B., V.D.M.), Istituto di Cibernetica (L.D.P.), and Istituto di Biochimica delle Proteine ed Enzimologia (P.O.), Consiglio Nazionale delle Ricerche, 80072 Arco Felice (NA); and Centro di Endocrinologia e Oncologia Sperimentale, Consiglio Nazionale delle Ricerche, and Dipartimento di Biologia e Patologia Cellulare e Molecolare, Università di Napoli Federico II (C.L., M.B.), 80131 Naples, Italy
Address all correspondence and requests for reprints to: Dr. Vincenzo Di Marzo, Istituto per la Chimica di Molecole di Interesse Biologico, Consiglio Nazionale delle Ricerche, 80072 Arco Felice (NA), Italy. E-mail: vdm@trinc.icmib.na.cnr.it.
Anandamide and 2-arachidonoylglycerol (2-AG), two endogenous ligands of the CB1 and CB2 cannabinoid receptor subtypes, inhibit the proliferation of PRL-responsive human breast cancer cells (HBCCs) through down-regulation of the long form of the PRL receptor (PRLr).
Here we report that 1) anandamide and 2-AG inhibit the nerve growth factor (NGF)-induced proliferation of HBCCs through suppression of the levels of NGF Trk receptors; 2) inhibition of PRLr levels results in inhibition of the proliferation of other PRL-responsive cells, the prostate cancer DU-145 cell line; and 3) CB1-like cannabinoid receptors are expressed in HBCCs and DU-145 cells and mediate the inhibition of cell proliferation and Trk/PRLr expression. ß-NGF-induced HBCC proliferation was potently inhibited (IC50 = 50–600 nM) by the synthetic cannabinoid HU-210, 2-AG, anandamide, and its metabolically stable analogs, but not by the anandamide congener, palmitoylethanolamide, or the selective agonist of CB2 cannabinoid receptors, BML-190. The effect of anandamide was blocked by the CB1 receptor antagonist, SR141716A, but not by the CB2 receptor antagonist, SR144528. Anandamide and HU-210 exerted a strong inhibition of the levels of NGF Trk receptors as detected by Western immunoblotting; this effect was reversed by SR141716A.
When induced by exogenous PRL, the proliferation of prostate DU-145 cells was potently inhibited (IC50 = 100–300 nM) by anandamide, 2-AG, and HU-210. Anandamide also down-regulated the levels of PRLr in DU-145 cells. SR141716A attenuated these two effects of anandamide. HBCCs and DU-145 cells were shown to contain 1) transcripts for CB1 and, to a lesser extent, CB2 cannabinoid receptors, 2) specific binding sites for [3H]SR141716A that could be displaced by anandamide, and 3) a CB1 receptor-immunoreactive protein. These findings suggest that endogenous cannabinoids and CB1 receptor agonists are potential negative effectors of PRL- and NGF-induced biological responses, at least in some cancer cells.
