Endocannabinoid system in cancer cachexia.

Image result for current opinion in clinical nutrition & metabolic care

“More than 60% of advanced cancer patients suffer from anorexia and cachexia.

This review focuses on the possible mechanisms by which the endocannabinoid system antagonizes cachexia-anorexia processes in cancer patients and how it can be tapped for therapeutic applications.

Cannabinoids stimulate appetite and food intake…

Cannabinoid type 1 receptor activation stimulates appetite and promotes lipogenesis and energy storage.

Further study of cancer-cachexia pathophysiology and the role of endocannabinoids will help us to develop cannabinoids without psychotropic properties, which will help cancer patients suffering from cachexia and improve outcomes of clinical antitumor therapy.”

http://www.ncbi.nlm.nih.gov/pubmed/17563462

The endocannabinoid signaling system in cancer.

Image result for trends in pharmacological sciences

“The endocannabinoid system, comprising lipid-derived endocannabinoids, their G-protein-coupled receptors (GPCRs), and the enzymes for their metabolism, is emerging as a promising therapeutic target in cancer.

This report highlights the main signaling pathways for the antitumor effects of the endocannabinoid system in cancer and its basic role in cancerpathogenesis, and discusses the alternative view of cannabinoid receptors as tumor promoters.

We focus on new players in the antitumor action of the endocannabinoid system and on emerging crosstalk among cannabinoid receptors and other membrane or nuclear receptors involved in cancer.”

http://www.ncbi.nlm.nih.gov/pubmed/23602129

5-Lipoxygenase and anandamide hydrolase (FAAH) mediate the antitumor activity of cannabidiol, a non-psychoactive cannabinoid.

“It has been recently reported that cannabidiol (CBD), a non-psychoactive cannabinoid, is able to kill glioma cells, both in vivo and in vitro, independently of cannabinoid receptor stimulation.

…the present investigation indicates that CBD exerts its antitumoral effects through modulation of the LOX pathway and of the endocannabinoid system…”

http://www.ncbi.nlm.nih.gov/pubmed/18028339

Cannabinoids inhibit peptidoglycan-induced phosphorylation of NF-κB and cell growth in U87MG human malignant glioma cells.

“Nuclear factor (NF)-κB is the key transcription factor involved in the inflammatory responses, and its activation aggravates tumors. Peptidoglycan (PGN), a main cell wall component of Gram-positive bacteria, stimulates Toll-like receptor 2 (TLR-2) and activates a number of inflammatory pathways, including NF-κB…

Cannabinoids have been reported to exert anti-inflammatory and antitumor effects…

Our finding that cannabinoids suppress the NF-κB inflammatory pathway and cell growth via CB1 receptors in glioma cells provides evidence for the therapeutic potential of targeting cannabinoid receptors for the treatment of inflammation-dependent tumor progression.”

http://www.ncbi.nlm.nih.gov/pubmed/22842590

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

“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/

Cannabidiol, a Non-Psychoactive Cannabinoid Compound, Inhibits Proliferation and Invasion in U87-MG and T98G Glioma Cells through a Multitarget Effect.

An external file that holds a picture, illustration, etc.
Object name is pone.0076918.g001.jpg

“…the non-psychoactive cannabinoid compound cannabidiol (CBD) effectively limits human glioma cell growth, both in vitro and in vivo… the present investigation confirms the antiproliferative and antiinvasive effects of CBD in U87-MG cells.

 More interestingly, these effects can also be extended to T98G glioma cells, a well known Δ9-THC-resistant lineage…

Taken together, these results provide new insights into the antitumor action of CBD, showing that this cannabinoid affects multiple tumoral features and molecular pathways.

 As CBD is a non-psychoactive phytocannabinoid that appears to be devoid of side effects, our results support its exploitation as an effective anti-cancer drug in the management of gliomas.”

 http://www.ncbi.nlm.nih.gov/pubmed/24204703

Full-text: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3804588/

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

“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

Critical appraisal of the potential use of cannabinoids in cancer management

“Cannabinoids have been attracting a great deal of interest as potential anticancer agents. Originally derived from the plant Cannabis sativa, there are now a number of endo-, phyto- and synthetic cannabinoids available. This review summarizes the key literature to date around the actions, antitumor activity, and mechanisms of action for this broad range of compounds…

Two therapeutic avenues exist for the development of cannabinoids as anticancer agents. As antiemetic and analgesic compounds, this class of compounds has been explored in terms of palliative care. More recently, cannabinoid agonists and antagonists have been screened for potential direct antitumorigenic properties.

… results suggest that overall the cannabinoids affect multiple cellular signaling pathways, which means they have the potential to decrease cancer development, growth, and metastasis.

Overall, the cannabinoids may show future promise in the treatment of cancer, but there are many significant hurdles to be overcome. There is much still to be learned about the action of the cannabinoids and the endocannabinoid system.

It is a distinct possibility that the cannabinoids may have a place in the future treatment of cancer.”

Full Text: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3770515/

Anticancer activity of anandamide in human cutaneous melanoma cells.

“Cannabinoids are implicated in the control of cell proliferation, but little is known about the role of the endocannabinoid system in human malignant melanoma. This study was aimed at characterizing the in vitro antitumor activity of anandamide (AEA) in A375 melanoma cells…

 Overall, these findings demonstrate that AEA induces cytotoxicity against human melanoma cells in the micromolar range of concentrations through a complex mechanism, which involve COX-2 and LOX-derived product synthesis and CB1 activation. Lipid raft modulation, probably linked to GPR55 activation, might also have a role.”

http://www.ncbi.nlm.nih.gov/pubmed/24041928

THC, found in cannabis, shown to be effective in the treatment of brain tumors

“In 2000, scientists at the Complutense University of Madrid carried out an extensive experiment, testing the effects of THC on cancerous brain cells in laboratory rats. Their discoveries were nothing short of amazing, as THC had effectively managed to destroy all cancer cells, while leaving healthy cells unaffected.
 
 Research into the effects of THC on glioblastoma would have had the potential to revolutionize available cancer treatments, yet due to insufficient funding and poor public exposure, the science team was unable to further their research.Manuel Guzman explained that “cannabinoids are selective antitumor compounds, as they can kill tumor cells without affecting their non-transformed counterparts.” In contrast to this, chemotherapy, the prevalent anticancer treatment of today, consists of a combination of antineoplastic drugs that have devastating physical and psychological side-effects… 
 
THC works by triggering the build-up of a chemical messenger known as ceramide, which in turn induces apoptosis (or programmed cell death) in mutated tumor cells.
Subsequent research into the properties of THC has revealed that it is among the very few naturally occurring, harmless substances that are capable of inducing programmed cell death in cancerous cells. Other substances with this property include anandamide, other cannabinoids and tumor necrosis factors produced by the immune system in its attempt to fight cancer.
 
After months of effort to obtain funding for testing the medical effects of THC on human tissues, the Madrid science team was forced to abandon this project, although there is currently no effective treatment available for malignant brain tumors.”