Document Detail


Cannabinoids induce cancer cell proliferation via tumor necrosis factor alpha-converting enzyme (TACE/ADAM17)-mediated transactivation of the epidermal growth factor receptor.
MedLine Citation:
PMID:  15026328     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Cannabinoids, the active components of marijuana and their endogenous counterparts were reported as useful analgetic agents to accompany primary cancer treatment by preventing nausea, vomiting, and pain and by stimulating appetite. Moreover, they have been shown to inhibit cell growth and to induce apoptosis in tumor cells. Here, we demonstrate that anandamide, Delta(9)-tetrahydrocannabinol (THC), HU-210, and Win55,212-2 promote mitogenic kinase signaling in cancer cells. Treatment of the glioblastoma cell line U373-MG and the lung carcinoma cell line NCI-H292 with nanomolar concentrations of THC led to accelerated cell proliferation that was completely dependent on metalloprotease and epidermal growth factor receptor (EGFR) activity. EGFR signal transactivation was identified as the mechanistic link between cannabinoid receptors and the activation of the mitogen-activated protein kinases extracellular signal-regulated kinase 1/2 as well as prosurvival protein kinase B (Akt/PKB) signaling. Depending on the cellular context, signal cross-communication was mediated by shedding of proAmphiregulin (proAR) and/or proHeparin-binding epidermal growth factor-like growth factor (proHB-EGF) by tumor necrosis factor alpha converting enzyme (TACE/ADAM17). Taken together, our data show that concentrations of THC comparable with those detected in the serum of patients after THC administration accelerate proliferation of cancer cells instead of apoptosis and thereby contribute to cancer progression in patients.
Authors:
Stefan Hart; Oliver M Fischer; Axel Ullrich
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cancer research     Volume:  64     ISSN:  0008-5472     ISO Abbreviation:  Cancer Res.     Publication Date:  2004 Mar 
Date Detail:
Created Date:  2004-03-17     Completed Date:  2004-04-08     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  2984705R     Medline TA:  Cancer Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1943-50     Citation Subset:  IM    
Affiliation:
Department of Molecular Biology, Max-Planck-Institute of Biochemistry, Am Klopferspitz 18A, D-82152 Martinsried, Germany.
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MeSH Terms
Descriptor/Qualifier:
ADAM Proteins
Apoptosis / drug effects*
Benzoxazines
Cannabinoids / pharmacology*
Cell Division / drug effects
Enzyme Activation / drug effects
Epidermal Growth Factor / metabolism
Glioblastoma / enzymology,  pathology
Glycoproteins / metabolism
Humans
Intercellular Signaling Peptides and Proteins / metabolism
Lung Neoplasms / enzymology,  pathology
Metalloendopeptidases / metabolism*
Mitogen-Activated Protein Kinase 1 / metabolism
Mitogen-Activated Protein Kinase 3
Mitogen-Activated Protein Kinases / metabolism
Morpholines / pharmacology
Naphthalenes / pharmacology
Phosphorylation
Proto-Oncogene Proteins / metabolism
RNA Interference
Receptor, Epidermal Growth Factor / genetics,  metabolism*
Signal Transduction
Tetrahydrocannabinol / analogs & derivatives*,  pharmacology
Transcriptional Activation*
Tumor Cells, Cultured
Chemical
Reg. No./Substance:
0/Benzoxazines; 0/Cannabinoids; 0/Glycoproteins; 0/Intercellular Signaling Peptides and Proteins; 0/Morpholines; 0/Naphthalenes; 0/Proto-Oncogene Proteins; 112924-45-5/HU 211; 117147-70-3/amphiregulin; 134959-51-6/Win 55212-2; 149176-25-0/heparin-binding EGF-like growth factor; 1972-08-3/Tetrahydrocannabinol; 62229-50-9/Epidermal Growth Factor; EC 2.7.10.1/Receptor, Epidermal Growth Factor; EC 2.7.11.24/Mitogen-Activated Protein Kinase 1; EC 2.7.11.24/Mitogen-Activated Protein Kinase 3; EC 2.7.11.24/Mitogen-Activated Protein Kinases; EC 3.4.24.-/ADAM Proteins; EC 3.4.24.-/Metalloendopeptidases; EC 3.4.24.-/tumor necrosis factor-alpha convertase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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