Document Detail

Cannabinoid derivatives induce cell death in pancreatic MIA PaCa-2 cells via a receptor-independent mechanism.
MedLine Citation:
PMID:  16500647     Owner:  NLM     Status:  MEDLINE    
Cannabinoids (CBs) are implicated in the control of cell survival in different types of tumors, but little is known about the role of CB system in pancreatic cancer. Herein, we investigated the in vitro antitumor activity of CBs and the potential role of their receptors in human pancreatic cancer cells MIA PaCa-2. Characterization tools used for this study included growth inhibition/cell viability analyses, caspase 3/7 induction, DNA fragmentation, microarray analysis and combination index-isobologram method. Our results demonstrate that CBs produce a significant cytotoxic effect via a receptor-independent mechanism. The CB1 antagonist N-(piperidin-1-1yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (AM251) was the most active compound with an IC50 of 8.6 +/- 1.3 microM after 72 h. AM251 induces apoptosis, causes transcriptional changes of genes in janus kinase/signal transducers and activators of transcription signaling network and synergistically interacts with the pyrimidine analogue, 5-fluorouracil. These findings exclude the involvement of CB receptors in the regulation of MIA PaCa-2 cell growth and put AM251 forward as a candidate for the development of novel compounds worthy to be tested in this type of neoplasia.
Stefano Fogli; Paola Nieri; Andrea Chicca; Barbara Adinolfi; Veronica Mariotti; Paola Iacopetti; Maria Cristina Breschi; Silvia Pellegrini
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Publication Detail:
Type:  Journal Article     Date:  2006-02-20
Journal Detail:
Title:  FEBS letters     Volume:  580     ISSN:  0014-5793     ISO Abbreviation:  FEBS Lett.     Publication Date:  2006 Mar 
Date Detail:
Created Date:  2006-03-17     Completed Date:  2006-06-07     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0155157     Medline TA:  FEBS Lett     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  1733-9     Citation Subset:  IM    
Department of Psychiatry, University of Pisa, Via Bonanno, 6, 56126 Pisa, PI, Italy.
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MeSH Terms
Antineoplastic Agents / pharmacology
Apoptosis / drug effects*
Cannabinoids / antagonists & inhibitors,  pharmacology*
Cell Line, Tumor
Cell Proliferation / drug effects
Inhibitory Concentration 50
Pancreatic Neoplasms / drug therapy,  pathology*
Piperidines / pharmacology
Pyrazoles / pharmacology
Receptors, Cannabinoid
Reg. No./Substance:
0/AM 251; 0/Antineoplastic Agents; 0/Cannabinoids; 0/Piperidines; 0/Pyrazoles; 0/Receptors, Cannabinoid

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