CB2 receptor agonist JWH133 activates AMPK to inhibit growth of C6 glioma cells

It has been reported that endocannabinoid receptor type 2 (CB2) agonist JWH133 inhibits the growth of C6 glioma cells, but the underlying mechanism has not yet been fully elucidated. We showed that JWH133 inhibited C6 cells growth, reduced cAMP production and inhibited PKA activity through CB2 receptor. Decrease of PKA activity stimulated CaMKKβ, and subsequently elevated phosphorylation of AMPKα at threonine 172 site. The activation of AMPKα induced changes of downstream proteins, including increase of P53 phosphorylation and P21 production, as well as decrease of mTOR phosphorylation, that eventually inhibited C6 cells growth.