Article

Endocannabinoids in endocrine and related tumours

Dipartimento di Scienze Farmaceutiche, Università di Salerno, 84084 Fisciano (Salerno), Italy IEOS, CNR Napoli, 80131 Napoli, Italy.
Endocrine Related Cancer (Impact Factor: 4.91). 07/2008; 15(2):391-408. DOI: 10.1677/ERC-07-0258
Source: PubMed

ABSTRACT The 'endocannabinoid system', comprising the cannabinoid CB1 and CB2 receptors, their endogenous ligands, endocannabinoids and the enzymes that regulate their biosynthesis and degradation, has drawn a great deal of scientist attention during the last two decades. The endocannabinoid system is involved in a broad range of functions and in a growing number of physiopathological conditions. Indeed, recent evidence indicates that endocannabinoids influence the intracellular events controlling the proliferation of numerous types of endocrine and related cancer cells, thereby leading to both in vitro and in vivo antitumour effects. In particular, they are able to inhibit cell growth, invasion and metastasis of thyroid, breast and prostate tumours. The chief events of endocannabinoids in cancer cell proliferation are reported highlighting the correspondent signalling involved in tumour processes: regulation of adenylyl cyclase, cyclic AMP-protein kinase-A pathway and MEK-extracellular signal-regulated kinase signalling cascade.

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    • "In addition to regulation through the ceramide pathway, cannabinoids exhibit a direct effect on cAMP levels through the regulation of adenylate cyclase, downregulation of protein kinase A, and a decrease in gene transcription.14,68,117 In hormone-responsive cancer cells, this leads to decreases in the expression of breast cancer-associated antigen 1, prostate-specific antigen, and the androgen receptor in breast and prostate cells, respectively.25,53 "
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    • "CB1 is preferentially expressed in the central nervous system (CNS), [3], [4], [5] CB2 is predominantly expressed by immune cells [6], however evidence demonstrated its presence in the CNS [7], [8], [9]. Increasing reports suggest a role of the endocannabinoid system in a variety of physiological and pathophysiological conditions, including immunomodulation, [10] pain, cancer, [11], [12], [13], [14] psychiatric disorders [15] and immune-mediated diseases of the CNS such as multiple sclerosis (MS) [16]. In particular, MS results in focal areas of inflammation containing immune cell infiltrates and demyelination, [17] the prevailing view is that CD4+ T cells initiate the disease producing pro-inflammatory cytokines that drive the inflammatory process. "
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    • "A family of unsaturated fatty acid derivatives, biologically synthesised by many tissues, has been termed “endocannabinoids” (EC), because they exert their effects acting as endogenous ligands for cannabinoid receptors. In the peripheral and neural tissues, they have been shown to modulate as paracrine or autocrine mediators, protein and nuclear factors involved in many physiological functions such as cell proliferation, differentiation and apoptosis [2]. N-arachidonoylethanolamide (anandamide, AEA) and 2-arachidonoylglycerol (2-AG) are the best characterized prototype members of two families of endocannabinoids, the fatty acid amides (NAEs) and the monoacylglycerols, respectively [3]. "
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