The endocannabinoid system and cancer: therapeutic implication

From the British Journal of Pharmacology

An excerpt:
Screen Shot 2018-12-03 at 4.05.08 PM.png“Several mechanisms are likely to underline the pro‐apoptotic effects of cannabinoids and explain their anti‐cancer effects. Cannabinoids induce de novo synthesis of ceramides, a family of lipid molecules composed of sphingosine and a fatty acid, found in the cell membrane. Synthesis of ceramide occurs via activation of the enzyme ceramide synthase and leads to downstream activation of an extracellular regulated kinase (ERK) signalling cascade. This process results in cell cycle arrest and apoptosis. Activation of either CB1 or CB2 receptors triggers the ceramide‐ERK signalling pathway to promote apoptosis. (Figure 1 above). The increase in ceramide can also activate the p38 mitogen‐activated protein kinase (p38MAPK) pathway which can lead to apoptosis through multiple mechanisms (i.e. through activation of cysteine proteases (i.e. caspases) or through cytochrome C release from mitochondria). The sustained activation of ERK also promotes the induction of cyclin kinase inhibitor (p27/KIP1) which modulates regulatory molecules of the cell cycle (cyclins, cdks) resulting in cell cycle arrest and apoptosis…”

To read the full paper, click here


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