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Istituto di chimica biomolecolare

Torna all'elenco Contributi in rivista anno 2013

Contributo in rivista

Tipo: Articolo in rivista

Titolo: Non-THC cannabinoids inhibit prostate carcinoma growth in vitro and in vivo: pro-apoptotic effects and underlying mechanisms

Anno di pubblicazione: 2013

Formato: Elettronico

Autori: Luciano De Petrocellis, Alessia Ligresti, Aniello Schiano Moriello, Mariagrazia Iappelli, Roberta Verde, Colin G. Stott, Luigia Cristino, Pierangelo Orlando and Vincenzo Di Marzo

Affiliazioni autori: Istituto di Cibernetica, Endocannabinoid Research Group, Consiglio Nazionale delle Ricerche, Pozzuoli, Italy ; Istituto di Chimica Biomolecolare, Endocannabinoid Research Group, Consiglio Nazionale delle Ricerche, Pozzuoli , Italy ; GW Pharma Ltd, Salisbury, UK ; Istituto di Biochimica delle Proteine, Endocannabinoid Research Group, Consiglio Nazionale delle Ricerche, Napoli, Italy

Autori CNR:


Lingua: inglese

Abstract: BACKGROUND AND PURPOSE: receptor activation induces prostate carcinoma cell (PCC) apoptosis, but cannabinoids other than ?(9) -tetrahydrocannabinol (THC), which lack potency 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 particular cannabinoids (BDS), on AR-positive (LNCaP and 22RV1) and -negative (DU-145 and PC-3) cells, by evaluating cell viability (MTT test), cell cycle arrest and apoptosis induction, by FACS scans, caspase 3/7 assays, DNA fragmentation and TUNEL, and size of xenograft tumours induced by LNCaP and DU-145 cells. KEY RESULTS: Cannabidiol (CBD) significantly inhibited cell viability. Other compounds became effective in cells deprived of serum for 24 h. Several BDS were more potent than the pure compounds in the presence of serum. CBD-BDS (i.p.) potentiated the effects of bicalutamide and docetaxel against LNCaP and DU-145 xenograft tumours and, given alone, reduced LNCaP xenograft size. CBD (1-10 M) induced apoptosis and induced markers of intrinsic apoptotic pathways (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 AND IMPLICATIONS: These data support the clinical testing of CBD against prostate carcinoma. LINKED ARTICLE This article is commented on by Pacher et al., pp. 76-78 of this issue. To view this commentary visit http://dx.doi.org/10.1111/j.1476-5381.2012.02121.x.

Lingua abstract: inglese

Pagine da: 79

Pagine a: 102


British journal of pharmacology Nature Publishing Group.
Paese di pubblicazione: Regno Unito
Lingua: inglese
ISSN: 1476-5381

Numero volume: 168

Numero fascicolo: 1

DOI: 10.1111/j.1476-538112.02027

Referee: S: Internazionale

Indicizzato da:

  • ISI Web of Science (WOS) [000312544900012]
  • Scopus [2-s2.0-84872555149]

Parole chiave:

  • prostate
  • cannabinoid
  • TRP channel
  • apoptosis
  • ROS

URL: http://onlinelibrary.wiley.com/doi/10.1111/j.1476-5381.2012.02027.x/suppinfo

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