Cannabinoid receptor‐independent actions of HU210 upon the viability and mobility of PC3 prostate cancer cells

Abstract

Both CB receptor‐dependent and independent effects of cannabinoids upon cancer cell viability have been reported in the literature. Here, we reexamined cannabinoid effects upon PC3 cell viability and mobility in view of recent data indicating that prostate cancer CB1 receptor expression is associated with disease severity and outcome (Chung et al., Eur J Cancer, in press).PCA experiments showed that the PC3 cells had measurable, but low CB1 receptor expression, and no clear expression of CB2 receptors. Cell viability experiments, using 1% FBS and incubation times of 1‐6 days, indicated that the CB receptor agonists CP55,940 (0.3 and 1 µM) and HU210 (1 µM), the 2‐AG synthesis inhibitors orlistat (1 µM) and RHC‐80267 (30 µM) and MAFP (0.1 and 1 µM, an inhibitor of 2‐AG metabolism) did not affect cell viability. In contrast 3 and 10 µM HU210 rapidly blocked cell viability. PC3 mobility was assayed at 1% FBS by following the ability of cells to repopulate a scratched area of the well. No effects of CP55,940, orlistat, RHC‐80267, MAFP and 2‐AG itself were seen, whilst HU210 (10 but not 1 µM) and cytochalasin D, which disrupts actin cytoskeletons, completely halted cell mobility. The effect of HU210, due to reduced cell viability, was not blocked by concomitant incubation with AM251 (1 µM) or AM630 (1 µM). Thus under the experimental conditions used here, no CB receptor‐dependent effects upon PC3 cell viability and mobility are seen.