Anti-tumoral action of cannabinoids: Involvement of sustained ceramide accumulation and extracellular signal-regulated kinase activation

@article{GalveRoperh2000AntitumoralAO,
  title={Anti-tumoral action of cannabinoids: Involvement of sustained ceramide accumulation and extracellular signal-regulated kinase activation},
  author={Ismael Galve-Roperh and Cristina S{\'a}nchez and Mar{\'i}a Luisa Blasco Cort{\'e}s and Teresa G{\'o}mez del Pulgar and M. Izquierdo and Manuel Guzm{\'a}n},
  journal={Nature Medicine},
  year={2000},
  volume={6},
  pages={313-319}
}
Δ9-Tetrahydrocannabinol, the main active component of marijuana, induces apoptosis of transformed neural cells in culture. Here, we show that intratumoral administration of Δ9-tetrahydrocannabinol and the synthetic cannabinoid agonist WIN-55,212-2 induced a considerable regression of malignant gliomas in Wistar rats and in mice deficient in recombination activating gene 2. Cannabinoid treatment did not produce any substantial neurotoxic effect in the conditions used. Experiments with two… 
Molecular Mechanisms Involved in the Antitumor Activity of Cannabinoids on Gliomas: Role for Oxidative Stress
TLDR
The anti-cancer properties that cannabinoids exert on gliomas are summarized and their potential action mechanisms that appear complex are discussed, involving modulation of multiple key cell signaling pathways and induction of oxidative stress in glioma cells.
Inhibition of tumor angiogenesis by cannabinoids
TLDR
It is shown that local administration of a nonpsychoactive cannabinoid to mice inhibits angiogenesis of malignant gliomas as determined by immunohistochemical analyses and vascular permeability assays.
The antitumor action of cannabinoids on glioma tumorigenesis.
TLDR
This work presents the available experimental and clinical data, to date, regarding the antitumor action of cannabinoids on the tumorigenesis of gliomas.
Cannabinoids and Gliomas
TLDR
The good safety profile of THC, together with its possible growth-inhibiting action on tumor cells, justifies the setting up of future trials aimed at evaluating the potential antitumoral activity of cannabinoids.
Stimulation of the midkine/ALK axis renders glioma cells resistant to cannabinoid antitumoral action
TLDR
Mdk is identified as a pivotal factor involved in the resistance of glioma cells to THC pro-autophagic and antitumoral action, and it is suggested that selective targeting of the Mdk/ALK axis could help to improve the efficacy of antitUMoral therapies for gliomas.
Cannabinoid Signaling in Glioma Cells.
TLDR
Beyond blocking of tumor cells proliferation cannabinoids inhibit invasiveness, angiogenesis and the stem cell-like properties of glioma cells, showing profound activity in the complex tumor microenvironment.
Cannabinoids and cell fate.
Arachidonylethanolamide Induces Apoptosis of Human Glioma Cells through Vanilloid Receptor‐1
TLDR
It is observed that AEA induced apoptosis in long-term and recently established glioma cell lines via aberrantly expressed vanilloid receptor-1 (VR1), which shows that the selective targeting of VR1 by AEA or more stable analogues is an attractive research area for the treatment of gliomas.
Cannabinoids inhibit glioma cell invasion by down-regulating matrix metalloproteinase-2 expression.
TLDR
Manipulation of MMP-2 expression by RNA interference and cDNA overexpression experiments proved that down-regulation of this MMP plays a critical role in THC-mediated inhibition of cell invasion and constitutes a new hallmark of cannabinoid antitumoral activity.
...
...

References

SHOWING 1-10 OF 54 REFERENCES
The endogenous cannabinoid anandamide inhibits human breast cancer cell proliferation.
TLDR
The data suggest that anandamide blocks human breast cancer cell proliferation through CB1-like receptor-mediated inhibition of endogenous Prolactin action at the level of prolactin receptor.
Molecular characterization of a peripheral receptor for cannabinoids
TLDR
The cloning of a receptor for cannabinoids is reported that is not expressed in the brain but rather in macrophages in the marginal zone of spleen, which helps clarify the non-psychoactive effects of cannabinoids.
Involvement of sphingomyelin hydrolysis and the mitogen-activated protein kinase cascade in the Delta9-tetrahydrocannabinol-induced stimulation of glucose metabolism in primary astrocytes.
TLDR
Results indicate that THC produces a cannabinoid receptor-mediated stimulation of astrocyte metabolism that seems to rely on sphingomyelin hydrolysis and MAPK stimulation.
1,25‐Dihydroxyvitamin D3 induces programmed cell death in a rat glioma cell line
TLDR
The results provide the first evidence for the existence of a programmed cell death triggered by 1,25(OH)2D3 in glioma cells and may provide a basis for the development of new therapeutic strategies.
Structure of a cannabinoid receptor and functional expression of the cloned cDNA
TLDR
The cloning and expression of a complementary DNA that encodes a G protein-coupled receptor that is involved in cannabinoid-induced CNS effects (including alterations in mood and cognition) experienced by users of marijuana are suggested.
Endocannabinoids: endogenous cannabinoid receptor ligands with neuromodulatory action
The Stimulation of Ketogenesis by Cannabinoids in Cultured Astrocytes Defines Carnitine Palmitoyltransferase I as a New Ceramide‐Activated Enzyme
TLDR
Results indicate that cannabinoids stimulate ketogenesis in astrocytes by a mechanism that may rely on CB1 receptor activation, sphingomyelin hydrolysis, and ceramide‐mediated activation of CPT‐I.
Formation and inactivation of endogenous cannabinoid anandamide in central neurons
TLDR
It is reported that anandamide is produced in and released from cultured brain neurons in a calcium ion-dependent manner when the neurons are stimulated with membrane-depolarizing agents, indicating that multiple biochemical pathways may participate in an andamide formation in brain tissue.
Evidence for the Lack of Involvement of Sphingomyelin Hydrolysis in the Tumor Necrosis Factor‐Induced Secretion of Nerve Growth Factor in Primary Astrocyte Cultures
TLDR
The data suggest that TNFα‐mediated up‐regulation of NGF occurs independently of ceramide generation, which indicates the existence of an indirect role of NF‐κB in the regulation of N GF synthesis.
...
...