Regulation of circulating endocannabinoids associated with cancer and metastases in mice and humans

It is well-established that cannabinoids exert palliative effects on some cancer-associated symptoms. In addition evidences obtained during the last fifteen years support that these compounds can reduce tumor growth in animal models of cancer. Cannabinoids have been shown to activate an ER-stress related pathway that leads to the stimulation of autophagy-mediated cancer cell death. In addition, cannabinoids inhibit tumor angiogenesis and decrease cancer cell migration. The mechanisms of resistance to cannabinoid anticancer action as well as the possible strategies to develop cannabinoid-based combinational therapies to fight cancer have also started to be explored. In this review we will summarize these observations (that have already helped to set the bases for the development of the first clinical studies to investigate the potential clinical benefit of using cannabinoids in anticancer therapies) and will discuss the possible future avenues of research in this area.

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“…pathology (Sailler et al, 2014). A similar situation has been proposed for cannabinoid receptors and endocannabinoid degrading enzymes.…”

Section: -Endocannabinoid System: Role In Tumor Generation and Progrmentioning

confidence: 56%

The use of cannabinoids as anticancer agents

Velasco

Hernández-Tiedra

Dávila

et al. 2016

Progress in Neuro-Psychopharmacology and Biological Psychiatry

141

101

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“…The EC system is involved in many pathophysiological processes, and its role in cancerogenesis has been postulated [33]. The cancer-associated dysregulation of the EC system might lead to measurable changes in circulating EC levels [34]. Here, we investigated the potential role of the EC system as a disease-specific circulating hallmark of rare MPN.…”

Section: Discussionmentioning

confidence: 99%

Disease-Specific Derangement of Circulating Endocannabinoids and N-Acylethanolamines in Myeloproliferative Neoplasms

Forte

Fanelli

Mezzullo

et al. 2020

IJMS

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Growing evidence highlights the endocannabinoid (EC) system involvement in cancer progression. Lipid mediators of this system are secreted by hematopoietic cells, including the ECs 2-arachidonoyl-glycerol (2AG) and arachidonoyl-ethanolamide (AEA), the 2AG metabolite 1AG, and members of N-acylethanolamine (NAE) family—palmitoyl-ethanolamide (PEA) and oleoyl-ethanolamide (OEA). However, the relevance of the EC system in myeloproliferative neoplasms (MPN) was never investigated. We explored the EC plasma profile in 55 MPN patients, including myelofibrosis (MF; n = 41), polycythemia vera (PV; n = 9), and essential thrombocythemia (ET; n = 5) subclasses and in 10 healthy controls (HC). AEA, PEA, OEA, 2AG, and 1AG plasma levels were measured by LC–MS/MS. Overall considered, MPN patients displayed similar EC and NAE levels compared to HC. Nonetheless, AEA levels in MPN were directly associated with the platelet count. MF patients showed higher levels of the sum of 2AG and 1AG compared to ET and PV patients, higher OEA/AEA ratios compared to HC and ET patients, and higher OEA/PEA ratios compared to HC. Furthermore, the sum of 2AG and 1AG positively correlated with JAK2V617F variant allele frequency and splenomegaly in MF and was elevated in high-risk PV patients compared to in low-risk PV patients. In conclusion, our work revealed specific alterations of ECs and NAE plasma profile in MPN subclasses and potentially relevant associations with disease severity.

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“…Also the expression of CB 1 and CB 2 receptors was found to increase in mantel cell lymphoma and fatty acid amide hydrolase (FAAH) expression was reduced when compared to non-malignant B-cells (Islam et al, 2003;Ek et al, 2002;Wasik et al, 2014). It has also been shown in both the mouse model of metastatic melanoma and in humans that the circulating endocannabinoid levels have been associated with an increase in disease progression (Sailler et al, 2014). Indeed many reports have shown that an increase in the level of endocannabinoids and their receptors correlates with tumour aggressiveness (Malfitano et al, 2011) and that cannabinoids can inhibit the growth of xenograft tumours Carracedo et al, 2006b;Sanchez et al, 2001a).…”

Section: Anti-tumour Effects Of Cannabinoidsmentioning

confidence: 99%

Cannabinoid pharmacology in cancer research: A new hope for cancer patients?

Javid

Phillips

Afshinjavid

et al. 2016

European Journal of Pharmacology

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Cannabinoids have been used for many centuries to ease pain and in the past decade, the endocannabinoid system has been implicated in a number of pathophysiological conditions, such as mood and anxiety disorders, movement disorders such as Parkinson's and Huntington's disease, neuropathic pain, multiple sclerosis, spinal cord injury, atherosclerosis, myocardial infarction, stroke, hypertension, glaucoma, obesity, and osteoporosis. Several studies have demonstrated that cannabinoids also have anti-cancer activity and as cannabinoids are usually well tolerated and do not produce the typical toxic effects of conventional chemotherapies, there is considerable merit in the development of cannabinoids as potential anticancer therapies. Whilst the presence of psychoactive effects of cannabinoids could prevent any progress in this field, recent studies have shown the value of the non-psychoactive components of cannabinoids in activating apoptotic pathways, inducing anti-proliferative and anti-angiogenic effects. The aforementioned effects are suggested to be through pathways such as ERK, Akt, mitogen-activated protein kinase (MAPK) pathways, phosphoinositide 3-kinase (PI3K) pathways and hypoxia inducible factor 1 (HIF1), all of which are important contributors to the hallmarks of cancer. Many important questions still remain unanswered or are poorly addressed thus necessitating further research at basic pre-clinical and clinical levels. In this review, we address these issues with a view to identifying the key challenges that future research needs to address.

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Regulation of circulating endocannabinoids associated with cancer and metastases in mice and humans

Cited by 52 publications

References 45 publications

The use of cannabinoids as anticancer agents

The use of cannabinoids as anticancer agents

Disease-Specific Derangement of Circulating Endocannabinoids and N-Acylethanolamines in Myeloproliferative Neoplasms

Cannabinoid pharmacology in cancer research: A new hope for cancer patients?

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