Cannabinoids and omega-3/6 endocannabinoids as cell death and anticancer modulators

Iain Brown, Maria G. Cascio, Dino Rotondo, Roger G. Pertwee, Steven D. Heys, Klaus W. J. Wahle*

*Corresponding author for this work

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

Cannabinoids-endocannaboids are possible preventatives of common diseases including cancers. Cannabinoid receptors (CB1/2, 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 CB1/2 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.

Original languageEnglish
Pages (from-to)80-109
Number of pages30
JournalProgress in Lipid Research
Volume52
Issue number1
Early online date25 Oct 2012
DOIs
Publication statusPublished - Jan 2013

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Endocannabinoids
Cannabinoids
Cell death
Modulators
Cell Death
Neoplasms
Peroxisome Proliferator-Activated Receptors
Tumors
Anti-Inflammatory Agents
Cannabinoid Receptor CB1
Cells
Apoptosis
Ligands
Autophagy
Cell Cycle Checkpoints
Oncology
Chemotherapy
Eicosanoids
NF-kappa B
Ceramides

ASJC Scopus subject areas

  • Cell Biology
  • Biochemistry

Cite this

Cannabinoids and omega-3/6 endocannabinoids as cell death and anticancer modulators. / Brown, Iain; Cascio, Maria G.; Rotondo, Dino; Pertwee, Roger G.; Heys, Steven D.; Wahle, Klaus W. J.

In: Progress in Lipid Research, Vol. 52, No. 1, 01.2013, p. 80-109.

Research output: Contribution to journalArticle

Brown, Iain ; Cascio, Maria G. ; Rotondo, Dino ; Pertwee, Roger G. ; Heys, Steven D. ; Wahle, Klaus W. J. / Cannabinoids and omega-3/6 endocannabinoids as cell death and anticancer modulators. In: Progress in Lipid Research. 2013 ; Vol. 52, No. 1. pp. 80-109.
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