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Non-THC cannabinoids counteract prostate carcinoma growth in vitro and in vivo: pro-apoptotic effects and underlying mechanisms.
MedLine Citation:
PMID:  22594963     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Background. Cannabinoid receptor activation induces prostate carcinoma cell (PCC) apoptosis, but plant cannabinoids other than Δ(9) -tetrahydrocannabinol (THC), which lack strong activity at cannabinoid receptors, have not been investigated. Some of these compounds antagonize transient receptor potential melastatin type-8 (TRPM8) channels, the expression of which is necessary for androgen receptor (AR)-dependent PCC survival. Experimental approach. We tested pure cannabinoids and extracts from Cannabis strains enriched in certain cannabinoids (BDS), on AR-positive (LNCaP and 22RV1) and -negative (DU-145 and PC-3) cells, by evaluating: 1) cell viability with the MTT test, 2) cell-cycle arrest and apoptosis induction, by FACS scans, caspase 3/7 assays, DNA fragmentation and TUNEL, and 3) size of xenograft tumors induced by LNCaP and DU-145 cells. Key results. Cannabidiol (CBD) exerted a significant inhibition of cell viability. Other compounds became efficacious in cells deprived of serum for 24 hours. Several BDS were more potent than pure compounds in the presence of serum. Intra-peritoneal CBD-BDS potentiated the effects of bicalutamide and docetaxel against LNCaP and DU-145 xenograft tumors, respectively, and per se reduced LNCaP xenograft size. CBD (1-10 µM) induced apoptosis and markers of intrinsic pathways thereof, i.e. PUMA and CHOP expression and intracellular Ca(2+) . In LNCaP cells, the pro-apoptotic effect of CBD was only partly due to TRPM8 antagonism and was accompanied by down-regulation of AR, p53 activation and elevation of reactive oxygen species. LNCaP cells differentiated to androgen-insensitive neuroendocrine-like cells were more sensitive to CBD-induced apoptosis. Conclusions. These data support the clinical testing of CBD against prostate carcinoma. © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.
Authors:
Luciano De Petrocellis; Alessia Ligresti; Aniello Schiano Moriello; Mariagrazia Iappelli; Roberta Verde; Colin G Stott; Luigia Cristino; Pierangelo Orlando; Vincenzo Di Marzo
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-5-18
Journal Detail:
Title:  British journal of pharmacology     Volume:  -     ISSN:  1476-5381     ISO Abbreviation:  -     Publication Date:  2012 May 
Date Detail:
Created Date:  2012-5-18     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7502536     Medline TA:  Br J Pharmacol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
© 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.
Affiliation:
Endocannabinoid Research Group, Consiglio Nazionale delle Ricerche, Istituto di Cibernetica, Istituto di Chimica Biomolecolare Istituto di Biochimica delle Proteine. GW Pharma Ltd., UK.
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