The antimitogenic effect of the cannabinoid receptor agonist WIN55212-2 on human melanoma cells is mediated by the membrane lipid raft

Here are reported the antiproliferative effects of the cannabinoid agonist WIN upon humanmelanoma cells expressing mRNA and protein for both CB1 and CB2 receptors. While WINexerted antimitogenic effects, selective CB1 or CB2 agonists were unable to reproduce sucheffects and selective CB1 and CB2 antagonists did not inhibit WIN-induced cell death. Cellstreated with WIN, preincubated with the lipid raft disruptor methylcyclodestrin, were rescuedfrom death. WIN induced activation of caspases and phosphorylation of ERK that wereattenuated in cultures treated with methylcyclodestrin.Membrane lipid raft complex-mediated antimitogenic effect of WIN in melanoma couldrepresents a potential targets for a melanoma treatment.