Articolo in rivista, 2012, ENG
Proto MC, Gazzerro P, Di Croce L, Santoro A, Malfitano AM, Pisanti S, Laezza C, Bifulco M.
Department of Pharmaceutical Sciences, University of Salerno, Fisciano, SA, Italy. Istituto di Endocrinologia e Oncologia Sperimentale, Consiglio Nazionale delle Ricerche (IEOS-CNR), Napoli 80131, Italy.
Increasing evidence suggest the role of the cannabinoid receptors in the control of cell survival or death and signalling pathways involved in tumour progression. Cancer cell lines are characterised by a subtle modulation of cannabinoid receptor levels which produces a modified responsiveness to specific ligands, but the molecular mechanisms underlying these events are poorly and partially understood. We previously provided evidence that the endocannabinoid anandamide (AEA) exerts anti-proliferative effect likely by modulation of the expression of genes involved in the cellular fate. In this study we focused on the role of the CB1 receptor, endocannabinoids and steroids in the mechanisms involved in colorectal cancer cell growth inhibition, in vitro. We demonstrated that, in DLD1 and SW620 cells, 17²-estradiol induced a specific and strong up-regulation of the CB1 receptor by triggering activation of the CB1 promoting region, localized at the exon 1 of the CNR1 gene. Moreover, treatment of DLD1 and SW620 cells with Met-F-AEA, a stable AEA-analogous, or URB597, a selective inhibitor of FAAH, induced up-regulation of CB1 expression by co-localization of PPAR³ and RXR± at the promoting region. Finally, increased availability of AEA, of both exogenous and endogenous sources, induced the expression of estrogen receptor-beta in both cell lines. Our results partially elucidated the role of endocannabinoid system in the molecular mechanisms enrolled by steroids in the inhibition of colon cancer cell growth and strongly suggested that targeting the endocannabinoid system could represent a promising tool to improve the efficacy of colorectal cancer treatments. J. Cell. Physiol. © 2011 Wiley-Liss, Inc.
Journal of cellular physiology (Print)
IEOS – Istituto per l'endocrinologia e l'oncologia "Gaetano Salvatore"
ID: 21375
Year: 2012
Type: Articolo in rivista
Creation: 2011-10-25 00:00:00.000
Last update: 2015-11-19 15:25:28.000
CNR authors
External IDs
CNR OAI-PMH: oai:it.cnr:prodotti:21375