Figure 3.

Molecular aspects of anti-cancer effects of CBD. The effect of CBD on glioblastoma is in part mediated through CB₁, CB₂ and TRPV1 receptors. This leads to the increased levels of cytochrome c, caspase 3 and ROS as well as decreased levels of glutathione and increase expression of ERK and mTOR. More downstream effects include: decrease in stemness due to the decrease in Id1, Sox2 and p-STAT3; decrease in cancer aggressiveness due to the decrease in pAkt; decrease in proliferation due to the decrease in Ki67. The effect on colon cancer is in part mediated through GPR55 which leads to the decrease in adhesion and migration. The effect on leukemia is mediated through CB₂ receptor which leads to inhibition of PARP, increased levels of Nox4 and p22phox and reduced levels of pp38MAPK, resulting in increased frequency of apoptosis. In cervical cancer and lung cancer, CBD activates CB₁, CB₂ and TRPV1 receptors leading in part to upregulation of COX-2. The proapoptotic activity of CBD in lung cancer is associated with the upregulation of COX-2 and activation of PPARγ by the COX-2-derived products PGD2 and 15d-PGJ2. CBD exposure also leads to upregulation of pp38 and pp42/44 which in turn likely upregulates the TIMP-1 expression. TIMP-1 forms inhibitory complexes with MMP-2 and MMP-9 leading to inhibition of cancer invasiveness.