Molecular Mechanism of Cannabinoids in Cancer Progression – PMC

47], and displays inverse agonism to human CB2RnHighlight:anti-cancer effects by inducing apoptosis and inhibiting cell migration, and metastasis in different cancer typesnSticky notes:Some of the CBD anti-cancer activitiesnHighlight:THC + CBD (at a 1:1 ratio), exerts a strong anti-tumoral action in glioma xenograftsnHighlight:cannabichromene (CBC) has anti-proliferative action in prostate cell lines, in colorectal cancer Caco-2 cells, and MDA-MB-231 and MCF-7 breast cancer cell lines.nSticky notes:Alternate cannabinoid anticancer effectsnHighlight:Cannabidivarin (CBVD) and cannabinol (CBN) have pro-apoptotic effects on human prostate cell lines.nHighlight:CBVD inhibits the growth of colon cancer cells while CBN does so in breast cancer cellsnHighlight:Cannabidiolic acid (CBDA) inhibited the invasivity of breast cancer cells and downregulated the c-fos and the COX-2nHighlight:Several studies have demonstrated that cannabinoids mediated cell cycle dysregulation and inhibition of proliferation in cancer cells.nHighlight:accumulation of cells in the G1 phase and decrease of cells in the S phase of the cell cycle,nHighlight:increase in the expression of p27 and a decrease of Cdk4nHighlight:downregulation of Cdk4nHighlight:inactivation of pRbnHighlight:stopped cell cycle in phase G0-G1 and significantly increased the expression levels of protein ataxia telangiectasia-mutated gene (ATM) and p53 and reduced p21, CDK2, and Cyclin E protein levelsnHighlight:cell cycle stops at the G2-M phase, by reduction of Cdc2 and induction of ROS synthesis, provoking cell deathnHighlight:Cannabinoids activate apoptosis either through CB1 or CB2 receptors.nHighlight:increased the protein levels of cleaved caspase-3 and caspase-9nHighlight:CBD increased Bax and decreased Bcl-2 expression levels, causing a reduction of the ratio of Bcl-2/BaxnHighlight:increase of mitochondrial membrane permeability and a decrease of mitochondrial transmembrane potentialnHighlight:CBD treatment increased NoxanHighlight:THC, via CB1R activation, inhibited both PI3K/Akt and RAS-MAPK/ERK survival pathwaysnHighlight:CBD inhibited the survival of both estrogen receptor-positive and estrogen receptor-negative breast cancer cell lines and induced apoptosis cell death in a concentration-dependent manner compared with MCF-10A cells, non-tumorigenic mammary cells.nHighlight:activation of caspase-8nHighlight:release of cytochrome c and SMAC into the cytosol, and increased levels of Fas-LnHighlight:, CBD enhanced ROS generationnSticky notes:Depletes GSH, similar to vitamin CnHighlight:CBD with THC, CBG, CBN—this combination is called C6—induced cell cycle block in G2 phasenSticky notes:“C6”nHighlight:increase in the levels of activated caspase-3 and a reduction in the levels of Bcl-2nHighlight:endocannabinoid treatment activated the Erk pathway and at the same time produced a decrease in the activation levels of the Akt pathwaynHighlight:THC via activation of CB1R induced ceramide accumulation and Raf1/ERK activationnHighlight:Autophagy is a mechanism that leads to the degradation of damaged cytoplasmic componentsnHighlight:diminishes intracellular glutathione levelsnHighlight:Cannabinoids can induce autophagy in several cell lines and mouse models of cancer.nHighlight:most important mechanism by which cannabinoids cause autophagy is the accumulation of ceramide in tumor cells.nSticky notes:KEY POINTnHighlight:accumulation of ceramide in the cell stimulates the stress response of the ER and the activation of different proteins CHOP, ATF-4, and p8, which promote the interaction of tribbles pseudokinase 3 (TRIB3) with Akt, causing the inhibition of the PI3K/AKT/mTOR pathwaynHighlight:The signaling pathway p8/ATF4/CHOP/TRIB3, followed by the inhibition of the PI3K/AKT/mTOR cascade, is probably the most important antitumoral mechanism of cannabinoids.nHighlight:direct inhibitor of mTORC1nHighlight:reduced levels of tau and amyloid proteins in the brainnHighlight:THC-CBD combination strongly augmented the levels of the cleaved LC3-II form and the LC3-II/LC3-I rationSticky notes:AutophagynnHighlight:Cannabinoids effects have been shown to have anticarcinogenic properties by inhibiting the migratory and invasive capacity of tumoral cellsnHighlight:reducing the activity and intracellular levels of the metalloproteases MMP2 and MMP9nHighlight:Cannabidiol (CBD) can induce cell death in multiple myeloma (MM)nHighlight:SPARC is a matricellular protein important in tissue remodeling and extracellular matrix deposition. The release of SPARC is prevented by WINnHighlight:increase the release of extracellular vesicles containing miR-29b1nHighlight:CBD-THC combination was able to reduce cell migration of the MMnHighlight:treatment of CBD/THC in combination with other chemotherapeutic drugs acts in a synergic way, suggesting their use in combinatory therapy in several types of human cancersnHighlight: poor prognosis of breast cancer is correlated with high levels of metalloproteasesnHighlight:Cannabinoids modulated MMP activity via inhibition of MMP2 and activation of the MMP9 gene.nHighlight:high levels of metalloprotease, amplification, or overexpression of the ERB2 gene have been found in the biopsies of breast tumorsnHighlight:inhibition of adhesion and migrationnHighlight:THC, via CB receptors, inhibited EGF-induced growth, chemotaxis, and chemoinvasionnHighlight:THC reduced the EGF-induced phosphorylation of ERK1/2, JNK1/2, and AKT, responsible for the reduced migration and invasion observed in lung cancer cellsnHighlight:growth of solid tumors is dependent on the generation of new vascular supplynHighlight:Cannabinoids, in cancer cell, can block the activation of the vascular endothelial growth factor (VEGF) pathway, which is an inducer of angiogenesisnHighlight:main ligand (VEGF) and the active forms of its main receptors (VEGFR1 and VEGFR2), are downregulated in skin carcinomas, gliomas, and thyroid carcinomas after cannabinoids treatmentnHighlight:decrease the formation of distant tumor masses in animal modelsnHighlight:inhibit adhesion, migration, and invasiveness of glioma, breast, lung, and cervical cancer cells in vitro culturenHighlight:modulation of extracellular proteases (MMP2) [] and their inhibitors such as tissue inhibitors of matrix metalloproteinases 1 (TIMP1)nHighlight:general role of the ceramide and p8 regulated pathway in the antitumor activity of cannabinoids that target CB1 and CB2 receptorsnHighlight:CBD, by acting independently of CB1 and CB2 receptors, produced an antitumor effect including the reduction of invasiveness and metastasis in different cancer animal modelsnHighlight:downregulation of the helix–loop–helix transcription factor inhibitor of DNA binding 1 (ID1)nHighlight:Acquisition of invasive traits by tumor cells involve specific phenotypic changes associated with epithelial to mesenchymal transition (EMT), and regulated transdifferentiation process in which carcinoma cells lose cell-to-cell junctions and cell polarity and acquire migratory and invasive propertiesnHighlight:cannabinoid agonist WINnHighlight:WIN treatment resulted in the downregulation of cyclooxygenase-2 (COX-2) expression and decreased the phosphorylation of AKT, and inhibited EMTnHighlight:JWH-015 treatment of A549 lung cancer cells co-cultured with M2 polarized macrophages reduced the expression of FAK, VCAM1, and MMP2nHighlight:JWH-015 decreased lung tumor lesions, tumor growth, and also inhibited macrophage recruitment and EMT to the tumor site via EGFRnHighlight:inhibiting EMT and downregulating matrix metalloproteinase 9 (MMP 9) gene expression in aggressive human EC cellsnHighlight:THC and CBD inhibited the proliferation and expression of EGFR in lung cancer cells, and CBD enforced the effect of THCnHighlight:THC and CBD (alone and/or in combination) affected proliferation, EMT, and migration in vitronHighlight:anandamide treatment upregulated epithelial markers, like E-cadherin with a concomitant decrease in protein levels of mesenchymal markers, including vimentin and SNAIL1n]]>

About Dr. Nathan Goodyear
About Dr. Nathan Goodyear

Dr. Nathan Goodyear, a medical doctor with years of experience in the field of integrative cancer care, has announced the launch of an online training program. This program, available on his new website, will provide individuals with access to video trainings led by Dr. Goodyear himself, covering a range of topics related to integrative cancer care. These trainings will include information on the latest research and techniques in the field, as well as guidance on how to incorporate these approaches into a patient’s overall cancer treatment plan. With this online program, Dr. Goodyear hopes to make his expertise and knowledge more widely accessible, and help more people understand the benefits of integrative cancer care.


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