Cannabinoids as anticancer drugs: current status of preclinical research | British Journal of Cancer

1 receptors are primarily localised in the central nervous systemnHighlight:CB2 receptors are mostly expressed on cells of the immune systemnHighlight:anandamide, AEAnHighlight:2-AGnHighlight:transient receptor potential vanilloid 1 (TRPV1)nHighlight:THC exhibits the properties of an agonist at the CB2 receptor and a partial agonist at the CB1 receptor [18], as well as an agonist at the G protein-coupled receptor (GPR) 55nHighlight:CBD has been demonstrated to have weaker affinities with Ki values in the micromolar range and non-competitive antagonistic effects at both CB1 and CB2 receptornHighlight:CBD shows a binding preference to the CB2 receptor [20] and an antagonistic effect at GPR55nHighlight:CBD, the compound has been shown to increase the transcriptional activity of peroxisome proliferator-activated receptor γ (PPARγ)nHighlight:EC-synthesising and -degrading enzymes.nHighlight:endocannabinoidome”nHighlight:sesquiterpene β-caryophyllene, a potent CB2 agonistnHighlight:β-caryophyllene showed antiproliferative and proapoptotic properties on various cancer cell lines [38, 39] and enhanced the cytostatic effects of classical chemotherapeutic agents such as doxorubicin [40] and sorafenibnHighlight:intracranially administered THC was safe nHighlight:antiproliferative, proapoptotic and proautophagicnHighlight:anti-invasive, antimetastatic, anti-epithelial-to-mesenchymal-transition and anti-angiogenic effectsnHighlight:inhibition of protein kinase B (Akt)nHighlight:cell cycle arrest at the G1/S transition via inhibition of the prosurvival protein Akt and hypophosphorylation of the retinoblastoma protein (pRb) tumour suppressor proteinnHighlight:inactivation of the Akt pathway is also involved in the antitumour activity of cannabinoids on human gastric cancer [46], non-small cell lung cancer [47] and hepatocellular carcinoma (HCC) cellsnHighlight:downregulation of cyclin-dependent kinase 1 (CDK1), induction of p21 [49], or induction of p27kip1, decrease in cyclin (CCN) A and E, degradation of cell division cycle 25 A (CDC25A) and inactivation of CDK2nHighlight:arrest cells in the G0/G1 phase via CB2 receptor-dependent signallingnHighlight:upregulation of p27 and a reduction in CDK4 expression and phosphorylated pRb (P-pRb)nHighlight:CBD appears to inhibit cancer cell proliferation primarily via apoptosis signallingnHighlight:peak plasma concentrations of THC after inhalation or oral administration do not indeed exceed 1 μM nHighlight:intratumoral administrationnHighlight:hardly any mitogenic effects can be observed in the case of CBDnHighlight:proapoptotic sphingolipid ceramidenHighlight:regressive effect based on anti-angiogenic effects through the downregulation of a number of proangiogenic parameters such as vascular endothelial growth factor (VEGF), placental growth factor (PlGF), angiopoietin-2 (Ang-2) [118, 119] and MMP-2 nHighlight:inhibition of Kras-activated signalling pathways by p21 activated kinase 1 (PAK1) after treatment of cells with CBD and THCnHighlight:Cannabinoids were found to reduce expression of programmed death ligand 1 (PD-L1) nHighlight:enhancing immune checkpoint blockade of pancreatic cancer cells nHighlight:proangiogenic factors such as VEGF after exposure to LPS was shown to be blocked by treatment with CB1 (ACEA) and CB2 agonists (JWH-133), which in turn led to decreased tumour growth via inhibition of angiogenesis nHighlight:THC causes inhibition of cancer growth in vivo due to its cannabinoid receptor-activating properties in the tumour microenvironment and not in the tumour itself. nHighlight:THC and CBD, which are currently being tested in some studies as combination, have been preclinically shown to enhance the effect of various cytostatics, such as for vinca alkaloids, cytarabine, doxorubicin, mitoxantrone, carmustine, temozolomide, bortezomib, carfilzomib and cisplatinnHighlight:CBD has also been shown to enhance the effect of cisplatin nHighlight:in vitro cytotoxicity of CBD in combination with cisplatin, 5-fluorouracil or paclitaxel nHighlight:synergistic effect of the combination of CBD and THC should also be mentioned here, which for example induces autophagy-dependent necrosis in multiple myeloma cellsnHighlight:more sensitive to ionising radiationnHighlight:Increased radiosensitivityn]]>

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.


Leave a Comment

Your email address will not be published. Required fields are marked *

Skip to content