Δ9-Tetrahydrocannabinol inhibits cell cycle progression by downregulation of E2F1 in human glioblastoma multiforme cells

Galanti, Gil; Fisher, Tamar; Kventsel, Iris; Shoham, Jacob; Gallily, Ruth; Mechoulam, Raphael; Lavie, Gad; Amariglio, Ninette; Rechavi, Gideon; Toren, Amos

doi:10.1080/02841860701678787

Cited by 54 publications

(48 citation statements)

References 19 publications

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“…Cannabinoids are in general associated with a reduced invasiveness for various tumor types. 17,19,20,25,37 In contrast, one study reported an increased invasiveness after treatment with cannabinoids in a cannabinoid receptor independent way. 38 The experiments conducted for the present study revealed differentiated effects of cannabinoids.…”

Section: Cannabinoids Change the Cell Motility And Affect The Cell Armentioning

confidence: 95%

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The influence of biomechanical properties and cannabinoids on tumor invasion

Hohmann

Grabiec

Ghadban

et al. 2016

Cell Adhesion & Migration

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Background: Cannabinoids are known to have an anti-tumorous effect, but the underlying mechanisms are only sparsely understood. Mechanical characteristics of tumor cells represent a promising marker to distinguish between tumor cells and the healthy tissue. We tested the hypothesis whether cannabinoids influence the tumor cell specific mechanical and migratory properties and if these factors are a prognostic marker for the invasiveness of tumor cells.Methods: 3 different glioblastoma cell lines were treated with cannabinoids and changes of mechanical and migratory properties of single cells were measured using atomic force microscopy and time lapse imaging. The invasiveness of cell lines was determined using a co-culture model with organotypic hippocampal slice cultures.Results: We found that cannabinoids are capable of influencing migratory and mechanical properties in a cell line specific manner. A network analysis revealed a correlation between a "generalized stiffness" and the invasiveness for all tumor cell lines after 3 and 4 d of invasion time: Conclusions: Here we could show that a "generalized stiffness" is a profound marker for the invasiveness of a tumor cell population in our model and thus might be of high clinical relevance for drug testing. Additionally cannabinoids were shown to be of potential use for therapeutic approaches of glioblastoma.

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Section: Cannabinoids Change the Cell Motility And Affect The Cell Armentioning

confidence: 95%

“…Most of the studies analyzing the effects of cannabinoids on tumor cells have focused on apoptosis [17][18][19] or cell cycle arrest. 18,20 Changes and disruptions of the cytoskeleton in a quantitative manner and thus mechanical parameters have been investigated only sparsely.…”

Section: Introductionmentioning

confidence: 99%

The influence of biomechanical properties and cannabinoids on tumor invasion

Hohmann

Grabiec

Ghadban

et al. 2016

Cell Adhesion & Migration

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“…Recently, the stress-associated transcription factor p8 was found to be critically involved in cannabinoidinduced apoptosis of cancer cells (19) as its down-regulation could rescue viability of various cancer cells (20,21). At the end of the signaling cascade, tumor cells either undergo cell cycle arrest (22,23) or apoptosis (9,24).…”

Section: Introductionmentioning

confidence: 99%

Cannabinoid receptor 1 is a potential drug target for treatment of translocation-positive rhabdomyosarcoma

Oesch

Walter

Wachtel

et al. 2009

Molecular Cancer Therapeutics

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Gene expression profiling has revealed that the gene coding for cannabinoid receptor 1 (CB1) is highly up-regulated in rhabdomyosarcoma biopsies bearing the typical chromosomal translocations PAX3/FKHR or PAX7/FKHR. Because cannabinoid receptor agonists are capable of reducing proliferation and inducing apoptosis in diverse cancer cells such as glioma, breast cancer, and melanoma, we evaluated whether CB1 is a potential drug target in rhabdomyosarcoma. Our study shows that treatment with the cannabinoid receptor agonists HU210 and Δ 9 -tetrahydrocannabinol lowers the viability of translocationpositive rhabdomyosarcoma cells through the induction of apoptosis. This effect relies on inhibition of AKT signaling and induction of the stress-associated transcription factor p8 because small interfering RNA-mediated down-regulation of p8 rescued cell viability upon cannabinoid treatment. Finally, treatment of xenografts with HU210 led to a significant suppression of tumor growth in vivo. These results support the notion that cannabinoid receptor agonists could represent a novel targeted approach for treatment of translocation-positive rhabdomyosarcoma.

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“…2-arachidonylglyceryl ether, a putative endocannabiniod, inhibits the cell cycle by arresting at the G 0 /G 1 phase and inhibiting nuclear translocation of NF-κB in prostate carcinoma cells [42]. Treatment with delta 9-tetrahydrocannabinol induces cell cycle arrest at the G 0 phase and downregulates the expression levels of E2F1 and cyclin A in glioblastoma [43]. Anandamide also induces S phase growth arrest by regulating cell cycle-regulating proteins, including Chk1, Cdc25A and Cdk2 in breast cancer cells [44].…”

Section: Activation Of Cbr Induces 14-3-3β-mediated Signalingmentioning

confidence: 99%

Cannabinoid receptor activation inhibits cell cycle progression by modulating 14-3-3β

Jung

Park

Ghil

2014

Cellular and Molecular Biology Letters

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Cannabinoids display various pharmacological activities, including tumor regression, anti-inflammatory and neuroprotective effects. To investigate the molecular mechanisms underlying the pharmacological effects of cannabinoids, we used a yeast two-hybrid system to screen a mouse brain cDNA library for proteins interacting with type 1 cannabinoid receptor (CB1R). Using the intracellular loop 3 of CB1R as bait, we identified 14-3-3β as an interacting partner of CB1R and confirmed their interaction using affinity-binding assays. 14-3-3β has been reported to induce a cell cycle delay at the G2/M phase. We tested the effects of cannabinoids on cell cycle progression in HeLa cells synchronized using a double-thymidine block-and-release protocol and found an increase in the population of G2/M phase cells. We further found that CB1R activation augmented the interaction of 14-3-3β with Wee1 and Cdc25B, and promoted phosphorylation of Cdc2 at Tyr-15. These results suggest that cannabinoids induce cell cycle delay at the G2/M phase by activating 14-3-3β.

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Δ9-Tetrahydrocannabinol inhibits cell cycle progression by downregulation of E2F1 in human glioblastoma multiforme cells

Cited by 54 publications

References 19 publications

The influence of biomechanical properties and cannabinoids on tumor invasion

The influence of biomechanical properties and cannabinoids on tumor invasion

Cannabinoid receptor 1 is a potential drug target for treatment of translocation-positive rhabdomyosarcoma

Cannabinoid receptor activation inhibits cell cycle progression by modulating 14-3-3β

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