R(+)-methanandamide-induced cyclooxygenase-2 expression in H4 human neuroglioma cells: possible involvement of membrane lipid rafts

Hinz, Burkhard; Ramer, Robert; Eichele, Karin; Weinzierl, Ulrike; Brune, Kay

doi:10.1016/j.bbrc.2004.09.095

Cited by 30 publications

(22 citation statements)

References 41 publications

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“…In the present study, we demonstrated that the effects of both AEA and 2-AG are mediated via cannabinoid receptorindependent mechanisms, consistent with previous observations (21)(22)(23)(24)(25)(26). In fact, both growth-promoting and growthsuppressing actions of cannabinoids in a number of tumor types are receptor-independent and in the majority of cases were shown to be via interaction with lipid raft structures in the plasma membrane and/or regulation of ceramide levels (23)(24)(25)(26)68) in complete agreement with the data presented here.…”

Section: Discussionsupporting

confidence: 93%

“…Endocannabinoids (21)(22)(23). Therefore, we evaluated whether the receptor-independent effects of AEA and 2-AG shown here are also mediated through lipid rafts.…”

Section: Endocannabinoid-induced Effects On Apoptosis and Cellmentioning

confidence: 99%

“…In addition to their cannabinoid receptor-mediated effects, endocannabinoids, and in particular AEA, are capable of mediating a plethora of receptor-independent cell signaling effects (21)(22)(23)(24)(25)(26), most of which are via an interaction with cholesterolrich microdomains of the cell membrane, also known as lipid rafts (21)(22)(23), and the synthesis of the raft-associated, sphingolipid moiety ceramide (24). These lipid rafts are thought to provide a platform for signaling molecules to concentrate and efficiently interact thereby facilitating the subsequent signal transduction process (27,28).…”

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confidence: 99%

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Opposing Actions of Endocannabinoids on Cholangiocarcinoma Growth

DeMorrow

Glaser

Francis

et al. 2007

Journal of Biological Chemistry

160

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Cholangiocarcinomas are devastating cancers of biliary origin with limited treatment options. Modulation of the endocannabinoid system is being targeted to develop possible therapeutic strategies for a number of cancers; therefore, we evaluated the effects of the two major endocannabinoids, anandamide and 2-arachidonylglycerol, on numerous cholangiocarcinoma cell lines. Although anandamide was antiproliferative and proapoptotic, 2-arachidonylglycerol stimulated cholangiocarcinoma cell growth. Specific inhibitors for each of the cannabinoid receptors did not prevent either of these effects nor did pretreatment with pertussis toxin, a G i/o protein inhibitor, suggesting that anandamide and 2-arachidonylglycerol did not exert their diametric effects through any known cannabinoid receptor or through any other G i/o protein-coupled receptor. Using the lipid raft disruptors methyl-␤-cyclodextrin and filipin, we demonstrated that anandamide, but not 2-arachidonylglycerol, requires lipid raft-mediated events to inhibit cellular proliferation. Closer inspection of the lipid raft structures within the cell membrane revealed that although anandamide treatment had no observable effect 2-arachidonylglycerol treatment effectively dissipated the lipid raft structures and caused the lipid raft-associated proteins lyn and flotillin-1 to disperse into the surrounding membrane. In addition, anandamide, but not 2-arachidonylglycerol, induced an accumulation of ceramide, which was required for anandamide-induced suppression of cell growth. Finally we demonstrated that anandamide and ceramide treatment of cholangiocarcinoma cells recruited Fas and Fas ligand into the lipid rafts, subsequently activating death receptor pathways. These findings suggest that modulation of the endocannabinoid system may be a target for the development of possible therapeutic strategies for the treatment of this devastating cancer.Cholangiocarcinomas are devastating cancers of intrahepatic and extrahepatic origin that are increasing in both their worldwide incidence and mortality rates (1, 2). The challenges posed by these often lethal biliary tract cancers are daunting; conventional treatment options are limited, and the only hope for long term survival is that of complete surgical resection of the tumor (1, 2). Conventional chemotherapy and radiation therapy are not effective in prolonging long term survival (1); therefore it is important to understand the cellular mechanisms of cholangiocarcinoma cell growth with a view to develop novel chemopreventive strategies.Marijuana and its derivatives have been used in medicine for many centuries, and presently there is an emerging renaissance in the study of the therapeutic effects of cannabinoids. Ongoing research is determining that regulation of the endocannabinoid system may be effective in the treatment of pain (3, 4), glaucoma (5), and neurodegenerative disorders such as Parkinson disease (6) and multiple sclerosis (7). In addition, cannabinoids might be effective antitumoral agents because of their abil...

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Section: Discussionsupporting

confidence: 93%

“…Endocannabinoids (21)(22)(23). Therefore, we evaluated whether the receptor-independent effects of AEA and 2-AG shown here are also mediated through lipid rafts.…”

Section: Endocannabinoid-induced Effects On Apoptosis and Cellmentioning

confidence: 99%

mentioning

confidence: 99%

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Opposing Actions of Endocannabinoids on Cholangiocarcinoma Growth

DeMorrow

Glaser

Francis

et al. 2007

Journal of Biological Chemistry

160

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“…With respect to the observed CB receptor dependency of COX-2 expression by both cannabinoids, our data contradict previous observations from our group showing a receptor-independent induction of COX-2 expression by both cannabinoids in human non-pigmented ciliary epithelial [11] and neuroglioma cells [27][28][29]42] and for MA in human cervical carcinoma cells [30]. Thus, dependent on the cell type, cannabinoids may use either receptor-dependent or -independent pathways to confer increased synthesis of A c c e p t e d M a n u s c r i p t 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 20 PGs which may on the one hand depend on extracellular activation of membrane-bound receptors and might otherwise rely on a lipid raft-dependent intracellular uptake [29].…”

Section: Confirmation Of the Proposed Antimigratory Mechanism By Use contrasting

confidence: 84%

“…Based on our previous investigations demonstrating cannabinoids as potent inductors of COX-2 expression in diverse cell types [11,[27][28][29][30][31]] and on the above mentioned interference of NSAIDs with the IOP-lowering action of cannabinoids, we were particularily interested in the role of COX-2 and one of its potential downstream targets, the tissue inhibitor of matrix metalloproteinases-1 (TIMP-1), in this process. Here we show that the antimigratory action of the phytocannabinoid THC and the stable endocannabinoid analogue MA on human TM cells is conferred by a COX-2-dependent upregulation of TIMP-1.…”

Section: Introductionmentioning

confidence: 99%

Cyclooxygenase-2 and tissue inhibitor of matrix metalloproteinases-1 confer the antimigratory effect of cannabinoids on human trabecular meshwork cells

Ramer

Hinz

2010

Biochemical Pharmacology

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To cite this version:Robert Ramer, Burkhard Hinz. Cyclooxygenase-2 AND tissue inhibitor of matrix metalloproteinases-1 confer the antimigratory effect of cannabinoids on human trabecular meshwork cells. Biochemical Pharmacology, Elsevier, 2010, 80 (6) This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 3 ABSTRACTCannabinoids have received considerable attention as potential antiglaucomatous drugs.

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Synergistic interaction of the cannabinoid and death receptor systems – a potential target for future cancer therapies?

Keresztes

Streicher

2017

FEBS Letters

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Edited by Lukas Alfons HuberCannabinoid receptors have been shown to interact with other receptors, including tumor necrosis factor receptor superfamily (TNFRS) members, to induce cancer cell death. When cannabinoids and death-inducing ligands (including TNF-related apoptosis-inducing ligand) are administered together, they have been shown to synergize and demonstrate enhanced antitumor activity in vitro. Certain cannabinoid ligands have been shown to sensitize cancer cells and synergistically interact with members of the TNFRS, thus suggesting that the combination of cannabinoids with death receptor (DR) ligands induces additive or synergistic tumor cell death. This review summarizes recent findings on the interaction of the cannabinoid and DR systems and suggests possible clinical co-application of cannabinoids and DR ligands in the treatment of various malignancies.

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R(+)-methanandamide-induced cyclooxygenase-2 expression in H4 human neuroglioma cells: possible involvement of membrane lipid rafts

Cited by 30 publications

References 41 publications

Opposing Actions of Endocannabinoids on Cholangiocarcinoma Growth

Opposing Actions of Endocannabinoids on Cholangiocarcinoma Growth

Cyclooxygenase-2 and tissue inhibitor of matrix metalloproteinases-1 confer the antimigratory effect of cannabinoids on human trabecular meshwork cells

Synergistic interaction of the cannabinoid and death receptor systems – a potential target for future cancer therapies?

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