The endogenous cannabinoid anandamide inhibits human breast cancer cell proliferation

Petrocellis, Luciano De; Melck, Dominique; Palmisano, A.; Bisogno, Tiziana; Laezza, Chiara; Bifulco, Maurizio; Marzo, Vincenzo Di

doi:10.1073/pnas.95.14.8375

Cited by 371 publications

(290 citation statements)

References 38 publications

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“…25 This effect of AEA was due to a CB1-like receptor-mediated inhibition of adenylate cyclase and activation of extracellular signal-regulated kinase (ERK). 26 The signalling pathways linked to these two enzymes led to a lower expression of both the high-molecular weight form of the prolactin receptor 25 and the high -affinity trk neurotrophin receptor in the cells, 27 thus resulting in growth arrest. The antitumor effect of AEA has been recently demonstrated also in vivo, where it implicates inhibition of the activity of the K-ras oncogene product, p21 ras , thereby leading to the inhibition of the ras cascade-dependent tumor growth.…”

Section: Involvement Of Aea and Congeners In Apoptosismentioning

confidence: 99%

The endocannabinoid system, anandamide and the regulation of mammalian cell apoptosis

2003

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Endocannabinoids are a new class of lipid mediators, which include amides, esters and ethers of long-chain polyunsaturated fatty acids. Anandamide (N-arachidonoylethanolamine; AEA) and 2-arachidonoylglycerol (2-AG) are the main endogenous agonists of cannabinoid receptors able to mimic several pharmacological effects of D-9-tetrahydrocannabinol, the active principle of Cannabis sativa preparations like hashish and marijuana. The pathways leading to the synthesis and release of AEA and 2-AG from neuronal and non-neuronal cells are still rather uncertain. Instead, it is known that the activity of AEA is limited by cellular uptake through a specific membrane transporter, followed by intracellular degradation by a fatty acid amide hydrolase. Together with AEA and congeners these proteins form the 'endocannabinoid system'. Here, the involvement of AEA in apoptosis and the underlying signal transduction pathways will be reviewed, along with the metabolic routes and the molecular targets of this endocannabinoid. Also, recent findings on the apoptotic potential of AEA for neuronal cell differentiation and brain development will be discussed. Cell Death and Differentiation (2003) 10, 946-955.

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Section: Involvement Of Aea and Congeners In Apoptosismentioning

confidence: 99%

The endocannabinoid system, anandamide and the regulation of mammalian cell apoptosis

2003

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“…This receptor is activated in response to endogenous ligands, which are mainly derivatives of polyunsaturated fatty acids, including anandamide (arachidonylethanolamide [AEA]) (20,21) and 2-arachidonoylglycerol (21,22). Several synthetic cannabinoids, such as HU210 (23,24) and WIN55,212-2 (24,25), have been confirmed as ligands of the CB 1 receptor. However, the effects of endogenous and synthetic cannabinoids differ (26).…”

Section: P Arkinson's Disease (Pd) Is a Common Neurodegenerativementioning

confidence: 99%

Cannabinoid Receptor Type 1 Protects Nigrostriatal Dopaminergic Neurons against MPTP Neurotoxicity by Inhibiting Microglial Activation

Chung

Bok

Huh

et al. 2011

The Journal of Immunology

106

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This study examined whether the cannabinoid receptor type 1 (CB1) receptor contributes to the survival of nigrostriatal dopaminergic (DA) neurons in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson’s disease. MPTP induced significant loss of nigrostriatal DA neurons and microglial activation in the substantia nigra (SN), visualized with tyrosine hydroxylase or macrophage Ag complex-1 immunohistochemistry. Real-time PCR, ELISA, Western blotting, and immunohistochemistry disclosed upregulation of proinflammatory cytokines, activation of microglial NADPH oxidase, and subsequent reactive oxygen species production and oxidative damage of DNA and proteins in MPTP-treated SN, resulting in degeneration of DA neurons. Conversely, treatment with nonselective cannabinoid receptor agonists (WIN55,212-2 and HU210) led to increased survival of DA neurons in the SN, their fibers and dopamine levels in the striatum, and improved motor function. This neuroprotection by cannabinoids was accompanied by suppression of NADPH oxidase reactive oxygen species production and reduced expression of proinflammatory cytokines from activated microglia. Interestingly, cannabinoids protected DA neurons against 1-methyl-4-phenyl-pyridinium neurotoxicity in cocultures of mesencephalic neurons and microglia, but not in neuron-enriched mesencephalic cultures devoid of microglia. The observed neuroprotection and inhibition of microglial activation were reversed upon treatment with CB1 receptor selective antagonists AM251 and/or SR14,716A, confirming the involvement of the CB1 receptor. The present in vivo and in vitro findings clearly indicate that the CB1 receptor possesses anti-inflammatory properties and inhibits microglia-mediated oxidative stress. Our results collectively suggest that the cannabinoid system is beneficial for the treatment of Parkinson’s disease and other disorders associated with neuroinflammation and microglia-derived oxidative damage.

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“…At doses at or above 10 mg/kg it acts as an agonist at central cannabinoid CB1 receptors, producing catalepsy and hypothermia (Costa et al 1999;Crawley et al 1993;Fride and Mechoulam 1993). It also acts at peripheral CB1 (De Petrocellis et al 1998) andvanillin receptors (De Petrocellis et al 2001), actions possibly related to its analgesic effects. Thus, although actions of CARB and AEA have not been fully characterized, there appears to be little overlap in their pharmacological or physiological effects besides gap junction inactivation.…”

mentioning

confidence: 99%

A Role for Electrotonic Coupling in the Striatum in the Expression of Dopamine Receptor-mediated Stereotypies,

Moore

Grace

2002

Neuropsychopharmacology

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Stimulation of dopamine (DA) receptors in the striatum evokes a number of alterations in motor behavior in rats, as well as causing several alterations in cellular physiology, including changes in membrane potential, cell excitability, afferent drive, and electrotonic coupling. One cellular property that is potently modulated by DA stimulation is electrotonic coupling, a process shown to subserve motor pattern generation. To examine whether electrotonic coupling plays a role in mediating a specific set of DA receptor-mediated motor behaviors, we tested the effects of two inhibitors of gap junction conductance, carbenoxolone (CARB) and anandamide (AEA), on apomorphine (APO)-induced motor responses. We then used intra-striatal infusions of CARB to determine the role of electrotonic coupling specifically in the ventral striatum in the expression of i.p.) significantly increased motor activity (a composite score) and the frequencies of oral and sniffing stereotypies. APO also disrupted grooming initiation and completion. APO-induced oral stereotypies were selectively blocked by systemic administration of CARB (7.0, 35.0 mg/kg Adaptive behaviors, both learned and spontaneous, consist of sequences of "micro" movements executed by closely-related muscle groups. There is evidence that the initiation and execution of individual movements, such as oral movements involved in feeding, as well as the linking of these movements into a behavioral sequence, depend upon neuronal networks within the Beninger et al. 1991;Braun and Chase 1986;Byrnes et al. 1994;Delfs and Kelley 1990). Thus, in the context of behavioral sequencing, the simple 'repetitive' stereotypy (Berridge and Aldridge 2000a) produced by D2 receptor over-stimulation in the striatum (Delfs and Kelley 1990) can be seen as the inability to release one 'simple' behavior in order to allow initiation of the next simple behavior in a normal, adaptive sequence (Pedro et al. 1994;Szechtman et al. 1999). One means by which neuronal networks may interact within the striatum is via communication among clusters of functionally related striatal neurons. Such a network interaction may be mediated via gap junctions. It is well-established that electrotonic transmission between developing neurons is important in the formation and stabilization of functional networks (Bannerman et al. 2000;Peinado et al. 1993;Roerig and Feller 2000). However, there is also evidence that in the adult brain, electrotonic coupling directly mediates forms of neuronal network activity (Bou-Flores and Berger 2001;Jefferys 1995;Perez Velazquez and Carlen 2000) which, in turn, contribute to rhythmic behavioral patterning (Bou-Flores and Berger 2001;Rothwell 1998). Thus, it is likely that motor patterning may involve activity within neuronal networks coordinated via gap junctions. In the striatum, cells express connexins, the protein building blocks of gap junctions (Belluardo et al. 2000;Bennett et al. 1999). Striatal neurons also exhibit dye coupling, the transfer of dye molecules between neurons thro...

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The endogenous cannabinoid anandamide inhibits human breast cancer cell proliferation

Abstract: ABSTRACT

Cited by 371 publications

References 38 publications

The endocannabinoid system, anandamide and the regulation of mammalian cell apoptosis

The endocannabinoid system, anandamide and the regulation of mammalian cell apoptosis

Cannabinoid Receptor Type 1 Protects Nigrostriatal Dopaminergic Neurons against MPTP Neurotoxicity by Inhibiting Microglial Activation

A Role for Electrotonic Coupling in the Striatum in the Expression of Dopamine Receptor-mediated Stereotypies,

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