Recently, CB1 and CB2 endocannabinoid receptor agonists have been shown to exert antitumor activity and, therefore, they are now studied as potential anticancer agents. To clarify mechanism(s) of this phenomenon, we investigated the expression of CB1 and CB2 receptors in colorectal cancer biopsies and cell lines DLD-1 and HT29, and the effects of their agonists - ACEA and the 3g, respectively - on cancer cell apoptosis and ceramide production. CB1 receptor was mainly expressed in normal colonic epithelium whereas CB2 receptor was more expressed in cancer. Activation of CB1 and, still more, of CB2 receptor induced apoptosis and increased ceramide levels in both cell lines. These effects were prevented by ceramide synthesis inhibition as well as by small interfering RNA-induced TNF-α gene knockdown. The CB2 agonist 3g also reduced growth of DLD-1 colorectal cancer cells transplanted in nude mice. Our data indicate that TNF-α mediates signal transduction between cannabinoid receptor activation and ceramide production and that either CB1 or CB2 receptor activation induces apoptosis via ceramide synthesis in colorectal cancer cells.
|Titolo:||Cannabinoid Receptor Activation Commits Colon Cancer Cells toApoptosis Via Tumor Necrosis Factor A-Induced Ceramide Synthesis|
|Anno di registrazione:||2008|
|Autori di Ateneo:|
|Autori:||L Papucci; S Capaccioli; F Cianchi; N Schiavone; M Lulli; M Donnini; A Lapucci; L Magnelli; E Masini|
|Appare nelle tipologie:||1c - Abstract su rivista|