Table 3.
Anticancer mechanisms of cannabinoids and their molecular targets
| Anticancer mechanisms | Cannabinoid(s) | Cancer type(s) | Pathways and targets | References |
|---|---|---|---|---|
| Apoptosis induction | Δ9-THC, CBD, CBG | Glioma, Breast, Prostate, Colorectal | Induction of ER stress and ROS production; Activation of CB1/CB2 receptors leading to ceramide synthesis | [10, 189] |
| Autophagy stimulation | Δ9-THC, WIN-55,212-2 | Glioma, Lymphoma | Modulation of mTOR/PI3K/AKT pathways; Induction via ceramide synthesis through CB1/CB2 receptor activation | [182] |
| Cell cycle arrest | WIN-55,212-2, R-(+)-MET | Various Cancers | Upregulation of p21 and p27; Inhibition of cdc2, cdk2, cyclin E and D | [217] |
| Anti-proliferation | Δ9-THC, CBD | Colorectal, Glioma | Inhibition of RAS/MAPK and PI3K/AKT pathways; Modulation via CB2 receptor leading to p21 and p27 expression | [116, 204–208] |
| Anti-angiogenesis | Δ9-THC, WIN-55,212-2 | Various Cancers | Inhibition of VEGF, Ang-2, and PLGF; Suppression of MMP9 and MMP2 via ceramide pathway | [163, 186] |
| Metastasis inhibition | CBD, CBG | Colon, Breast, Glioma | Suppression of tumor cell migration and invasion; Regulation of cannabinoid-induced migration inhibition | [211, 215, 216] |
Abbreviations: 2-AG 2-Arachidonoylglycerol, AEA Anandamide, AKT Protein Kinase B, Ang-2 Angiopoietin-2, ATF4 Activating Transcription Factor 4, CB1R Cannabinoid Receptor Type 1, CB2R Cannabinoid Receptor Type 2, CBD Cannabidiol, CBDA Cannabidiolic Acid, CBG Cannabigerol, cdk Cyclin-Dependent Kinase, CHOP C/EBP Homologous Protein, DAG Diacylglycerol, ER Endoplasmic Reticulum, ERK1/2 Extracellular Signal-Regulated Kinases 1 and 2, GSK3β Glycogen Synthase Kinase 3 Beta, MAPK Mitogen-Activated Protein Kinase, mTOR Mechanistic Target of Rapamycin, MMP Matrix Metalloproteinase, PI3K Phosphoinositide 3-Kinase, PLGF Placental Growth Factor, pRb Retinoblastoma Protein, ROS Reactive Oxygen Species, THC Δ9-Tetrahydrocannabinol, TRIB3 Tribbles Pseudokinase 3, TRPM8 Transient Receptor Potential Cation Channel Subfamily M Member 8, TRPV1 Transient Receptor Potential Vanilloid 1, TRPV2 Transient Receptor Potential Vanilloid 2, VEGF Vascular Endothelial Growth Factor