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Cannabinoids and omega-3/6 endocannabinoids as cell death and anticancer modulators.
Prog Lipid Res. 2013 Jan; 52(1):80-109.PL

Abstract

Cannabinoids-endocannaboids are possible preventatives of common diseases including cancers. Cannabinoid receptors (CB(½), TRPV1) are central components of the system. Many disease-ameliorating effects of cannabinoids-endocannabinoids are receptor mediated, but many are not, indicating non-CBR signaling pathways. Cannabinoids-endocannabinoids are anti-inflammatory, anti-proliferative, anti-invasive, anti-metastatic and pro-apoptotic in most cancers, in vitro and in vivo in animals. They signal through p38, MAPK, JUN, PI3, AKT, ceramide, caspases, MMPs, PPARs, VEGF, NF-κB, p8, CHOP, TRB3 and pro-apoptotic oncogenes (p53,p21 waf1/cip1) to induce cell cycle arrest, autophagy, apoptosis and tumour inhibition. Paradoxically they are pro-proliferative and anti-apoptotic in some cancers. Differences in receptor expression and concentrations of cannabinoids in cancer and immune cells can elicit anti- or pro-cancer effects through different signal cascades (p38MAPK or PI3/AKT). Similarities between effects of cannabinoids-endocannabinoids, omega-3 LCPUFA and CLAs/CLnAs as anti-inflammatory, antiangiogenic, anti-invasive anti-cancer agents indicate common signaling pathways. Evidence in vivo and in vitro shows EPA and DHA can form endocannabinoids that: (i) are ligands for CB(½) receptors and possibly TRPV-1, (ii) have non-receptor mediated bioactivity, (iii) induce cell cycle arrest, (iii) increase autophagy and apoptosis, and (iv) augment chemotherapeutic actions in vitro. They can also form bioactive, eicosanoid-like products that appear to be non-CBR ligands but have effects on PPARs and NF-kB transcription factors. The use of cannabinoids in cancer treatment is currently limited to chemo- and radio-therapy-associated nausea and cancer-associated pain apart from one trial on brain tumours in patients. Further clinical studies are urgently required to determine the true potential of these intriguing, low toxicity compounds in cancer therapy. Particularly in view of their synergistic effects with chemotherapeutic agents similar to that observed for n-3 LCPUFA.

Authors+Show Affiliations

University of Aberdeen, School of Medicine and Dentistry, Cancer Medicine Research Group, Aberdeen, United Kingdom.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

23103355

Citation

Brown, Iain, et al. "Cannabinoids and Omega-3/6 Endocannabinoids as Cell Death and Anticancer Modulators." Progress in Lipid Research, vol. 52, no. 1, 2013, pp. 80-109.
Brown I, Cascio MG, Rotondo D, et al. Cannabinoids and omega-3/6 endocannabinoids as cell death and anticancer modulators. Prog Lipid Res. 2013;52(1):80-109.
Brown, I., Cascio, M. G., Rotondo, D., Pertwee, R. G., Heys, S. D., & Wahle, K. W. (2013). Cannabinoids and omega-3/6 endocannabinoids as cell death and anticancer modulators. Progress in Lipid Research, 52(1), 80-109. https://doi.org/10.1016/j.plipres.2012.10.001
Brown I, et al. Cannabinoids and Omega-3/6 Endocannabinoids as Cell Death and Anticancer Modulators. Prog Lipid Res. 2013;52(1):80-109. PubMed PMID: 23103355.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cannabinoids and omega-3/6 endocannabinoids as cell death and anticancer modulators. AU - Brown,Iain, AU - Cascio,Maria G, AU - Rotondo,Dino, AU - Pertwee,Roger G, AU - Heys,Steven D, AU - Wahle,Klaus W J, Y1 - 2012/10/26/ PY - 2012/10/05/received PY - 2012/10/05/accepted PY - 2012/10/30/entrez PY - 2012/10/30/pubmed PY - 2013/7/16/medline SP - 80 EP - 109 JF - Progress in lipid research JO - Prog. Lipid Res. VL - 52 IS - 1 N2 - Cannabinoids-endocannaboids are possible preventatives of common diseases including cancers. Cannabinoid receptors (CB(½), TRPV1) are central components of the system. Many disease-ameliorating effects of cannabinoids-endocannabinoids are receptor mediated, but many are not, indicating non-CBR signaling pathways. Cannabinoids-endocannabinoids are anti-inflammatory, anti-proliferative, anti-invasive, anti-metastatic and pro-apoptotic in most cancers, in vitro and in vivo in animals. They signal through p38, MAPK, JUN, PI3, AKT, ceramide, caspases, MMPs, PPARs, VEGF, NF-κB, p8, CHOP, TRB3 and pro-apoptotic oncogenes (p53,p21 waf1/cip1) to induce cell cycle arrest, autophagy, apoptosis and tumour inhibition. Paradoxically they are pro-proliferative and anti-apoptotic in some cancers. Differences in receptor expression and concentrations of cannabinoids in cancer and immune cells can elicit anti- or pro-cancer effects through different signal cascades (p38MAPK or PI3/AKT). Similarities between effects of cannabinoids-endocannabinoids, omega-3 LCPUFA and CLAs/CLnAs as anti-inflammatory, antiangiogenic, anti-invasive anti-cancer agents indicate common signaling pathways. Evidence in vivo and in vitro shows EPA and DHA can form endocannabinoids that: (i) are ligands for CB(½) receptors and possibly TRPV-1, (ii) have non-receptor mediated bioactivity, (iii) induce cell cycle arrest, (iii) increase autophagy and apoptosis, and (iv) augment chemotherapeutic actions in vitro. They can also form bioactive, eicosanoid-like products that appear to be non-CBR ligands but have effects on PPARs and NF-kB transcription factors. The use of cannabinoids in cancer treatment is currently limited to chemo- and radio-therapy-associated nausea and cancer-associated pain apart from one trial on brain tumours in patients. Further clinical studies are urgently required to determine the true potential of these intriguing, low toxicity compounds in cancer therapy. Particularly in view of their synergistic effects with chemotherapeutic agents similar to that observed for n-3 LCPUFA. SN - 1873-2194 UR - https://www.unboundmedicine.com/medline/citation/23103355/Cannabinoids_and_omega_3/6_endocannabinoids_as_cell_death_and_anticancer_modulators_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0163-7827(12)00053-7 DB - PRIME DP - Unbound Medicine ER -