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 human melanoma cells expressing mRNA and protein for both CB1 and CB2 receptors. While WIN exerted antimitogenic effects, selective CB1 or CB2 agonists were unable to reproduce such effects and selective CB1 and CB2 antagonists did not inhibit WIN-induced cell death. Cells treated with WIN, preincubated with the lipid raft disruptor methylcyclodestrin, were rescued from death. WIN induced activation of caspases and phosphorylation of ERK that were attenuated in cultures treated with methylcyclodestrin.Membrane lipid raft complex-mediated antimitogenic effect of WIN in melanoma could represents a potential targets for a melanoma treatment.

► WIN induces apoptosis in melanoma cells which express both CB1 and CB2 receptors.
► Selective CB1 or CB2 agonists were unable to reproduce WIN effects.
► Selective CB1 and CB2 antagonists did not inhibit WIN-induced cell death.
► WIN activates caspases and pERK which were blunt in cells treated with MCD.
► WIN exerts antimitogenic effect upon melanoma cells via a mechanism involving lipid raft.