Pharmacological inhibition of MAGL attenuates experimental colon carcinogenesis

Pagano, Ester; Borrelli, Francesca; Orlando, Pierangelo; Romano, Barbara; Monti, Martina; Morbidelli, Lucia; Aviello, Gabriella; Imperatore, Roberta; Capasso, Raffaele; Piscitelli, Fabiana; Buono, Lorena; Marzo, Vincenzo Di; Izzo, Angelo A.

doi:10.1016/j.phrs.2017.02.002

Cited by 52 publications

(66 citation statements)

References 53 publications

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“…For instance, JZL184 was reported to reduce cancer cells growth, induce apoptosis, and prevent invasion in vitro [279,282] as well as suppress osteolytic bone metastasis and alleviate cachexia and bone mass loss in rodents (8-16 mg/kg) [283]. Another MAGL inhibitor, URB602 (5mg/kg), suppressed progression of colon cancer in mice [284].…”

Section: Cancermentioning

confidence: 99%

A Guide to Targeting the Endocannabinoid System in Drug Design

Stasiulewicz

Znajdek

Grudzień

et al. 2020

IJMS

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The endocannabinoid system (ECS) is one of the most crucial systems in the human organism, exhibiting multi-purpose regulatory character. It is engaged in a vast array of physiological processes, including nociception, mood regulation, cognitive functions, neurogenesis and neuroprotection, appetite, lipid metabolism, as well as cell growth and proliferation. Thus, ECS proteins, including cannabinoid receptors and their endogenous ligands’ synthesizing and degrading enzymes, are promising therapeutic targets. Their modulation has been employed in or extensively studied as a treatment of multiple diseases. However, due to a complex nature of ECS and its crosstalk with other biological systems, the development of novel drugs turned out to be a challenging task. In this review, we summarize potential therapeutic applications for ECS-targeting drugs, especially focusing on promising synthetic compounds and preclinical studies. We put emphasis on modulation of specific proteins of ECS in different pathophysiological areas. In addition, we stress possible difficulties and risks and highlight proposed solutions. By presenting this review, we point out information pivotal in the spotlight of ECS-targeting drug design, as well as provide an overview of the current state of knowledge on ECS-related pharmacodynamics and show possible directions for needed research.

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Section: Cancermentioning

confidence: 99%

A Guide to Targeting the Endocannabinoid System in Drug Design

Stasiulewicz

Znajdek

Grudzień

et al. 2020

IJMS

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“…The inhibition of the MAGL enzyme with the consequent increase of 2‐AG levels was also reported to decrease tumour growth, exerting an anti‐angiogenic activity. In vivo studies reported that MAGL inhibitors down‐regulated pro‐angiogenic factors, particularly VEGF and FGF‐2, and also reduced the number of vessels (Pagano et al, ).…”

Section: Involvement Of the Endocannabinoid System In Tumour Progressionmentioning

confidence: 99%

Insights into the effects of the endocannabinoid system in cancer: a review

Fraguas-Sánchez

Martín-Sabroso

Torres-Suárez

2018

British J Pharmacology

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In the last few decades, the endocannabinoid system has attracted a great deal of interest in terms of its applications to clinical medicine. In particular, its applications in cancer probably represent one of the therapeutic areas with most promise. On the one hand, expression of the endocannabinoid system is altered in numerous types of tumours, compared to healthy tissue, and this aberrant expression has been related to cancer prognosis and disease outcome, suggesting a role of this system in tumour growth and progression that depends on cancer type. On the other hand, cannabinoids exert an anticancer activity by inhibiting the proliferation, migration and/or invasion of cancer cells and also tumour angiogenesis. However, some cannabinoids, at lower concentrations, may increase tumour proliferation, inducing cancer growth. Enough data has been provided to consider the endocannabinoid system as a new therapeutic target in cancer, although further studies to fully establish the effect of cannabinoids on tumour progression are still needed.

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“…The molecular basis of this interaction is not yet known at the moment. High expression of monoacylglycerol lipase (MAGL), responsible for the production of free fatty acids, is observed in highly malignant colon cancer cells [83,84]. This fact combined with the physiological role of FABP5, consisting of transporting free fatty acids to the appropriate cell compartments, prompts to seek the answer to the question whether FABP5 and MAGL come into functional interaction with each other, and if so, how does this affect CRC progression.…”

Section: Fabps: Fatty Acid-binding Proteinsmentioning

confidence: 99%

Important players in carcinogenesis as potential targets in cancer therapy: an update

2020

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The development of cancer is a problem that has accompanied mankind for years. The growing number of cases, emerging drug resistance, and the need to reduce the serious side effects of pharmacotherapy are forcing scientists to better understand the complex mechanisms responsible for the initiation, promotion, and progression of the disease. This paper discusses the modulation of the particular stages of carcinogenesis by selected physiological factors, including: acetylcholine (ACh), peroxisome proliferator-activated receptors (PPAR), fatty acid-binding proteins (FABPs), Bruton's tyrosine kinase (Btk), aquaporins (AQPs), insulin-like growth factor-2 (IGF-2), and exosomes. Understanding their role may contribute to the development of more effective and safer therapies based on new binding sites.

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Pharmacological inhibition of MAGL attenuates experimental colon carcinogenesis

Cited by 52 publications

References 53 publications

A Guide to Targeting the Endocannabinoid System in Drug Design

A Guide to Targeting the Endocannabinoid System in Drug Design

Insights into the effects of the endocannabinoid system in cancer: a review

Important players in carcinogenesis as potential targets in cancer therapy: an update

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