Cannabinoids induce glioma stem-like cell differentiation and inhibit gliomagenesis.

Posted on January 26, 2014 by David

“Glioma stem-like cells constitute one of the potential origins of gliomas, and therefore, their elimination is an essential factor for the development of efficient therapeutic strategies.

Cannabinoids are known to exert an antitumoral action on gliomas that relies on at least two mechanisms: induction of apoptosis of transformed cells and inhibition of tumor angiogenesis…

The discovery of an endogenous cannabinoid system, together with the great improvement in our understanding of the signaling mechanisms responsible for cannabinoid actions, has fostered the interest in the potential therapeutic applications of cannabinoids.

Several studies have demonstrated a significant antitumoral action of cannabinoid ligands in animal models. Thus, cannabinoid administration to nude mice curbs the growth of different tumors, including gliomas…

Cannabinoids are known to exert an antitumoral action against gliomas…

Overall, our results demonstrate that cannabinoids target glioma stem-like cells, promote their differentiation, and inhibit gliomagenesis, thus giving further support to their potential use in the management of malignant gliomas.

In conclusion, our results demonstrate the action of cannabinoids on glioma stem-like cells and thus may open new avenues for cannabinoid-based antitumoral strategies.”

http://www.jbc.org/content/282/9/6854.long

Molecular Mechanisms Involved in the Antitumor Activity of Cannabinoids on Gliomas: Role for Oxidative Stress.

Posted on November 29, 2013 by David

“Cannabinoids, the active components of Cannabis sativa, have been shown to exert antiproliferative and proapoptotic effects on a wide spectrum of tumor cells and tissues.

Of interest, cannabinoids have displayed great potency in reducing the growth of glioma tumors, one of the most aggressive CNS tumors, either in vitro or in animal experimental models curbing the growth of xenografts generated by subcutaneous or intrathecal injection of glioma cells in immune-deficient mice.

Cannabinoids appear to be selective antitumoral agents as they kill glioma cells without affecting the viability of non-transformed cells.

This review will summarize the anti-cancer properties that cannabinoids exert on gliomas and discuss their potential action mechanisms that appear complex, involving modulation of multiple key cell signaling pathways and induction of oxidative stress in glioma cells.” http://www.ncbi.nlm.nih.gov/pubmed/24281104

“The therapy of gliomas, the most frequent class of malignant primary brain tumors and one of the most aggressive forms of cancer characterized by high invasiveness, a high proliferation rate and rich neovascularization, could benefit from the use of cannabinoids, the active compounds of Cannabis sativa, and their synthetic derivatives. They have been shown to mimic the endogenous substances named “endocannabinoids” that activate specific cannabinoid receptors (CB1 and CB2).

Cannabinoids have been proven to inhibit glioma tumor growth in either in vitro or in vivo models through several cellular pathways such as elevating ceramide levels, modulating PI3K/Akt, MAPK kinases, inducing autophagy and oxidative stress state in glioma cells, thus arresting cell proliferation and inducing apoptosis. Since cannabinoids kill tumor cells without toxicity on their non transformed counterparts, probably modulating the cell survival/cell death pathways differently, they can represent a class of new potential anticancer drugs.” http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3835116/

http://www.thctotalhealthcare.com/category/gllomas/

Systematic review of the literature on clinical and experimental trials on the antitumor effects of cannabinoids in gliomas.

Posted on October 23, 2013 by David

“To evaluate, through a systematic review of the literature, the antitumoral effects of cannabinoids on gliomas…

In all experimental studies included, cannabinoids exerted antitumoral activity in vitro and/or antitumoral evidence in vivo in several models of tumor cells and tumors.

The antitumor activity included: antiproliferative effects (cell cycle arrest), decreased viability and cell death by toxicity, apoptosis, necrosis, autophagy, as well as antiangiogenic and antimigratory effects.

Antitumoral evidence included: reduction in tumor size, antiangiogenic, and antimetastatic effects.

Additionally, most of the studies described that the canabinnoids exercised selective antitumoral action in several distinct tumor models. Thereby, normal cells used as controls were not affected.

The safety factor in the cannabinoids’ administration has also been demonstrated in vivo.

The various cannabinoids tested in multiple tumor models showed antitumoral effects both in vitro and in vivo.

These findings indicate that cannabinoids are promising compounds for the treatment of gliomas.”

http://www.ncbi.nlm.nih.gov/pubmed/24142199

Cannabidiol, a non-psychoactive cannabinoid compound, affects metalloproteinases and pro-survival intracellular pathways in u87-mg human glioma cell line

Posted on October 22, 2013 by David

“Malignant gliomas are the most common primary brain tumors… Recently, we have shown that the non-psychoactive cannabinoid compound cannabidiol (CBD) induced apoptosis of human glioma cells in vitro and tumor regression in vivo…the present study was to investigate the anti-migratory action of CBD…

In conclusion, the present investigation adds further insights into the antitumoral action of the non-psychoactive CBD, showing multiple mechanisms through which the cannabinoid inhibits glioma cell growth and motility.

As CBD is a natural compound without psychotropic and side effects, these data lead us to consider CBD as a new potential anticancer drug useful in the management of gliomas.”

http://air.unimi.it/handle/2434/142533

Marijuana Compounds Possess Synergistic Anti-Cancer Effects, Study Says

Posted on August 1, 2013 by David

“Marijuana’s active compounds act synergistically to inhibit the growth of cancer cells and induce malignant cell death, according to preclinical trial data published online by the journal Molecular Cancer Therapeutics.

Investigators at the University of California, Pacific Medical Center Research Institute assessed whether the administration of the non-psychoactive cannabidiol would enhance the anti-cancer effects of THC on glioblastoma (brain cancer) cells.

Researchers reported that a combination of cannabinoids showed greater anti-cancer activity than the administration of either compound individually. “We discovered that cannabidiol enhanced the ability of THC to inhibit cell proliferation and induce cell cycle arrest and apoptosis (programmed cell death),” authors reported.

Investigators concluded: “Individually, THC and cannabidiol can activate distinct pathways in glioblastoma cells that ultimately culminate in inhibition of cancer cell growth and invasion as well as induction of cell death. We hypothesized that, if the individual agents were combined, a convergence on shared pathways may ensue, leading to an enhanced ability of the combination treatment to inhibit certain cancer cell phenotypes. We found this to be true in this investigation.”

A 2008 scientific review published in the journal Cancer Research reported that the cannabinioids inhibit cell proliferation in a wide range of cancers, including brain cancer, prostate cancer, breast cancer, lung cancer, skin cancer, pancreatic cancer, and lymphoma.”

http://norml.org/news/2010/01/21/marijuana-compounds-possess-synergistic-anti-cancer-effects-study-says

Marijuana Ingredient Inhibits VEGF Pathway Required For Brain Tumor Blood Vessels

Posted on July 31, 2013 by David

“Cannabinoids, the active ingredients in marijuana, restrict the sprouting of blood vessels to brain tumors by inhibiting the expression of genes needed for the production of vascular endothelial growth factor (VEGF).

“Blockade of the VEGF pathway constitutes one of the most promising antitumoral approaches currently available,” said Manuel Guzmán, professor of biochemistry and molecular biology, with the Complutense University in Madrid, Spain, and the study’s principal investigator.

“The present findings provide a novel pharmacological target for cannabinoid-based therapies.””

More: http://www.sciencedaily.com/releases/2004/08/040816085401.htm

“Cannabinoids inhibit the vascular endothelial growth factor pathway in gliomas.” http://cancerres.aacrjournals.org/content/64/16/5617.long

Amphiregulin is a factor for resistance of glioma cells to cannabinoid-induced apoptosis.

Posted on July 18, 2013 by David

“Gliomas, one of the most malignant forms of cancer, exhibit high resistance to conventional therapies. Identification of the molecular mechanisms responsible for this resistance is therefore of great interest to improve the efficacy of the treatments against these tumors. Delta9-Tetrahydrocannabinol (THC), the major active ingredient of marijuana, and other cannabinoids inhibit tumor growth in animal models of cancer, including glioma, an effect that relies, at least in part, on the ability of these compounds to induce apoptosis of tumor cells.

…we identified the epidermal growth factor receptor ligand amphiregulin as a candidate factor to mediate the resistance of glioma cells to cannabinoid treatment… in vivo silencing of amphiregulin rendered the resistant tumors xenografts sensitive to cannabinoid antitumoral action.

Amphiregulin expression was associated with increased extracellular signal-regulated kinase (ERK) activation, which mediated the resistance to THC by blunting the expression of p8 and TRB3-two genes involved in cannabinoid-induced apoptosis of glioma cells.

Our findings therefore identify Amphirregulin as a factor for resistance of glioma cells to THC-induced apoptosis and contribute to unraveling the molecular bases underlying the emerging notion that targeted inhibition of the EGFR pathway can improve the efficacy of antitumoral therapies.”

http://www.ncbi.nlm.nih.gov/pubmed/19229996

Stimulation of the midkine/ALK axis renders glioma cells resistant to cannabinoid antitumoral action

Posted on July 18, 2013 by David

“Δ⁹-Tetrahydrocannabinol (THC), the major active ingredient of marijuana, and other cannabinoids inhibit tumor growth in animal models of cancer, including glioma, an effect that relies, at least in part, on the stimulation of autophagy-mediated apoptosis in tumor cells.

…Altogether, our findings identify Mdk as a pivotal factor involved in the resistance of glioma cells to THC pro-autophagic and antitumoral action, and suggest that selective targeting of the Mdk/ALK axis could help to improve the efficacy of antitumoral therapies for gliomas.”

Full text: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3131933/

Poly-ε-caprolactone microspheres as a drug delivery system for cannabinoid administration: development, characterization and in vitro evaluation of their antitumoral efficacy.

Posted on June 19, 2013 by David

“Cannabinoids show promise for the treatment of various medical conditions such as emesis, anorexia, pain, cancer, multiple sclerosis, Parkinson’s disease and glaucoma.

The objective of the present work was to assess the feasibility of developing cannabinoid loaded poly-ε-caprolactone (PCL) microparticles prepared by the oil-in-water emulsion-solvent evaporation technique as a suitable dosage form for their administration.

In vitro cell viability studies demonstrated the antitumoral activity of CBD released from microparticles. After 4 and 7 days of incubation, CBD in microspheres significantly inhibited the growth of MDA-MB-231 cells by 60% as compared to the 50% attained with free drug.

The results suggest that PCL microparticles could be an alternative delivery system for long-term cannabinoid administration, showing potential therapeutic advantages over free drug.”

http://www.ncbi.nlm.nih.gov/pubmed/22580111

Preparation and characterization of Δ9-tetrahydrocannabinol-loaded biodegradable polymeric microparticles and their antitumoral efficacy on cancer cell lines.

Posted on June 19, 2013 by David

“Cannabinoids present an interesting therapeutic potential as antiemetics, appetite stimulants in debilitating diseases (cancer, AIDS and multiple sclerosis), analgesics, and in the treatment of multiple sclerosis and cancer, among other conditions.

However, despite their high clinical potential, only few dosage forms are available to date. In this paper, the development of Δ⁹-tetrahydrocannabinol (THC) biodegradable microspheres as an alternative delivery system for cannabinoid parenteral administration is proposed. Tetrahydrocannabinol was encapsulated into biodegradable microspheres by the oil-in-water (o/w) emulsion solvent evaporation method. Several formulations were prepared using different drug:polymer ratios. The influence of antioxidant (α-tocopherol acetate) concentration on the release of THC from the microparticles was studied. Elevated process yield and entrapment efficiencies were achieved.The in vitro drug release studies showed that the encapsulated drug was released over a two week period.

As THC has shown therapeutic potential as anticancer drug, the efficacy of the microspheres was tested on different cancer cell lines.

Interestingly, the microspheres were able to inhibit cancer cell proliferation during the nine-day study period.

All the above results suggest that the use of biodegradable microspheres would be a suitable alternative delivery system for THC administration.”

http://www.ncbi.nlm.nih.gov/pubmed/23773072