Cannabinoids, endocannabinoids, and cancer

Hermanson, Daniel J.; Marnett, Lawrence J.

doi:10.1007/s10555-011-9318-8

Cited by 140 publications

(123 citation statements)

References 133 publications

(185 reference statements)

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“…Anandamide is known to mediate its effects through cannabinoid receptor CB1 [7, 30]. Hence, the expression of FAAH and CB1 were assessed in the NSCLC cell lines- A459, A549, CALU1, H460 and H1299 (Fig 1A).…”

Section: Resultsmentioning

confidence: 99%

“…CB1 receptor is mainly expressed in the brain and CNS whereas CB2 receptor is expressed in immune system [4-6]. The use of cannabinoid agonists as anti-cancer agents has proven successful in various in vitro and in vivo cancer models such as glioma, breast, prostate, colon, leukemia and lymphoid tumors [7-10]. They have been shown to modulate various cell survival pathways such as the extracellular signal-related kinase (ERK), phosphoinositide 3-kinase (PI3K), p38 mitogen-activated protein kinase (p38 MAPK), protein kinase B (AKT) and ceramide pathways [11-13].…”

Section: Introductionmentioning

confidence: 99%

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FAAH inhibition enhances anandamide mediated anti-tumorigenic effects in non-small cell lung cancer by downregulating the EGF/EGFR pathway

et al. 2014

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The endocannabinoid anandamide (AEA), a neurotransmitter was shown to have anti-cancer effects. Fatty acid amide hydrolase (FAAH) metabolizes AEA and decreases its anti-tumorigenic activity. In this study, we have analyzed the role of FAAH inhibition in non-small cell lung cancer (NSCLC). We have shown that FAAH and CB1 receptor which is activated by AEA are expressed in lung adenocarcinoma patient samples and NSCLC cell lines A549 and H460. Since the synthetic analogue of anandamide (Met-F-AEA) did not possess significant anti-tumorigenic effects, we used Met-F-AEA in combination with FAAH inhibitor URB597 which significantly reduced EGF (epidermal growth factor)-induced proliferative and chemotactic activities in vitro when compared to anti-tumorigenic activity of Met-F-AEA alone. Further analysis of signaling mechanisms revealed that Met-F-AEA in combination with URB597 inhibits activation of EGFR and its downstream signaling ERK, AKT and NF-kB. In addition, it inhibited MMP2 secretion and stress fiber formation. We have also shown that the Met-F-AEA in combination with URB597 induces G0/G1 cell cycle arrest by downregulating cyclin D1 and CDK4 expressions, ultimately leading to apoptosis via activation of caspase-9 and PARP. Furthermore, the combination treatment inhibited tumor growth in a xenograft nude mouse model system. Tumors derived from Met-F-AEA and URB597 combination treated mice showed reduced EGFR, AKT and ERK activation and MMP2/MMP9 expressions when compared to Met-F-AEA or URB597 alone. Taken together, these data suggest in EGFR overexpressing NSCLC that the combination of Met-F-AEA with FAAH inhibitor resulted in superior therapeutic response compared to individual compound activity alone.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

FAAH inhibition enhances anandamide mediated anti-tumorigenic effects in non-small cell lung cancer by downregulating the EGF/EGFR pathway

et al. 2014

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“…In the last several years, development of new CBR ligands has become an intense area in cancer research because of the role of the endocannabinoid system in the regulation of cell proliferation and apoptosis (Oesch and Gertsch, 2009;Guindon and Hohmann, 2011;Hermanson and Marnett, 2011). In considering the overall influence of CBRs on MNF signaling, it is clear that CBR-directed signaling has the potential to be much more complex than initially thought, because it depends not only on which CBRs are present (CB 1 R versus CB 2 R), but also on the multiplicity of active and intermediate states of each receptor.…”

Section: Discussionmentioning

confidence: 99%

Cannabinoid Receptor Activation Correlates with the Proapoptotic Action of the β₂-Adrenergic Agonist (R,R′)-4-Methoxy-1-Naphthylfenoterol in HepG2 Hepatocarcinoma Cells

Paul

Ramamoorthy

Scheers

et al. 2012

J Pharmacol Exp Ther

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Inhibition of cell proliferation by fenoterol and fenoterol derivatives in 1321N1 astrocytoma cells is consistent with ␤ 2 -adrenergic receptor (␤ 2 -AR) stimulation. However, the events that result in fenoterol-mediated control of cell proliferation in other cell types are not clear. Here, we compare the effect of the ␤ 2 -AR agonists (R,RЈ)-fenoterol (Fen) and (R,RЈ)-4-methoxy-1-naphthylfenoterol (MNF) on signaling and cell proliferation in HepG2 hepatocarcinoma cells by using Western blotting and [ 3 H]thymidine incorporation assays. Despite the expression of ␤ 2 -AR, no cAMP accumulation was observed when cells were stimulated with isoproterenol or Fen, although the treatment elicited both mitogen-activated protein kinase and phosphatidylinositol 3-kinase/Akt activation. Unexpectedly, isoproterenol and Fen promoted HepG2 cell growth, but MNF reduced proliferation together with increased apoptosis. The mitogenic responses of Fen were attenuated by 3-(isopropylamino)-1-[(7-methyl-4-indanyl)oxy]butan-2-ol (ICI 118,551), a ␤ 2 -AR antagonist, whereas those of MNF were unaffected. Because of the coexpression of ␤ 2 -AR and cannabinoid receptors (CBRs) and their impact on HepG2 cell proliferation, these G␣ i /G␣ o -linked receptors may be implicated in MNF signaling. Cell treatment with (R)-(ϩ)-[2,3-dihydro-5-methyl-3-(4-morpholinylmethyl)pyrrolo[1,2,3-de]-1,4-benzoxazin-6-yl]-1-napthalenylmethanone (WIN 55,212-2), a synthetic agonist of CB 1 R and CB 2 R, led to growth inhibition, whereas inverse agonists of these receptors blocked MNF mitogenic responses without affecting Fen signaling. MNF responses were sensitive to pertussis toxin. The ␤ 2 -ARdeficient U87MG cells were refractory to Fen, but responsive to the antiproliferative actions of MNF and WIN 55,212-2. The data indicate that the presence of the naphthyl moiety in MNF results in functional coupling to the CBR pathway, providing one of the first examples of a dually acting ␤ 2 -AR-CBR ligand.

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“…Numerous studies carried out during the past few years have demonstrated that cannabinoids exhibit antitumor effects in different cancer cell lines [38] and in a wide range of animal models. [39,40] In particular, the cytotoxic effect of AEA has been extensively investigated in the C6 cell line.…”

Section: Effect Of Aea and Analogues On Glioma C6 Cell Viabilitymentioning

confidence: 99%

Improved Enzymatic Procedure for the Synthesis of Anandamide and N‐Fatty Acylalkanolamine Analogues: A Combination Strategy to Antitumor Activity

et al. 2015

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Twenty N-fatty acylamines from linolenic and arachidonic acids, fifteen of them new compounds, were obtained through Candida antarctica B lipase-catalyzed esterification and aminolysis reactions in very good yields and with high chemoselectivity. The optimal reaction conditions were achieved by studying the reaction parameters (temperature, E/S ratio, alcohol and alkanolamine/fatty acid ratio, time, solvent, free-solvent system, etc.). To identify ideal enzymatic methods for generating the alkanolamides we evaluated enzyme performance in three procedures: i) aminolysis of ethyl ester, ii) direct condensation between the fatty acid and the alkanolamine, and iii) a

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Cannabinoids, endocannabinoids, and cancer

Cited by 140 publications

References 133 publications

FAAH inhibition enhances anandamide mediated anti-tumorigenic effects in non-small cell lung cancer by downregulating the EGF/EGFR pathway

FAAH inhibition enhances anandamide mediated anti-tumorigenic effects in non-small cell lung cancer by downregulating the EGF/EGFR pathway

Cannabinoid Receptor Activation Correlates with the Proapoptotic Action of the β₂-Adrenergic Agonist (R,R′)-4-Methoxy-1-Naphthylfenoterol in HepG2 Hepatocarcinoma Cells

Improved Enzymatic Procedure for the Synthesis of Anandamide and N‐Fatty Acylalkanolamine Analogues: A Combination Strategy to Antitumor Activity

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Cannabinoids, endocannabinoids, and cancer

Cited by 140 publications

References 133 publications

FAAH inhibition enhances anandamide mediated anti-tumorigenic effects in non-small cell lung cancer by downregulating the EGF/EGFR pathway

FAAH inhibition enhances anandamide mediated anti-tumorigenic effects in non-small cell lung cancer by downregulating the EGF/EGFR pathway

Cannabinoid Receptor Activation Correlates with the Proapoptotic Action of the β2-Adrenergic Agonist (R,R′)-4-Methoxy-1-Naphthylfenoterol in HepG2 Hepatocarcinoma Cells

Improved Enzymatic Procedure for the Synthesis of Anandamide and N‐Fatty Acylalkanolamine Analogues: A Combination Strategy to Antitumor Activity

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Cannabinoid Receptor Activation Correlates with the Proapoptotic Action of the β₂-Adrenergic Agonist (R,R′)-4-Methoxy-1-Naphthylfenoterol in HepG2 Hepatocarcinoma Cells