Arachidonylethanolamide induces apoptosis of human glioma cells through vanilloid receptor-1.

Posted on May 7, 2015 by David

“The anti-tumor properties of cannabinoids have recently been evidenced, mainly with delta9-tetrahydrocannabinol (THC).

Here we investigated whether the most potent endogenous cannabinoid, arachidonylethanolamide (AEA), could be a candidate.

We observed that AEA induced apoptosis in long-term and recently established glioma cell lines via aberrantly expressed vanilloid receptor-1 (VR1).

In contrast with their role in THC-mediated death, both CB1 and CB2 partially protected glioma against AEA-induced apoptosis.

These data show that the selective targeting of VR1 by AEA or more stable analogues is an attractive research area for the treatment of glioma.”

http://www.ncbi.nlm.nih.gov/pubmed/15453094

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

It’s “BRAIN TUMOR AWARENESS MONTH”. Please, BE AWARE:

Posted on May 2, 2015 by David

“A glioma is a primary brain tumor that originates from the supportive cells of the brain, called glial cells.” http://neurosurgery.ucla.edu/body.cfm?id=159

“Long-term use of both mobile and cordless phones is associated with an increased risk for glioma, the most common type of brain tumor, the latest research on the subject concludes.” http://www.medscape.com/viewarticle/834888

“Remarkably, cannabinoids kill glioma cells selectively and can protect non-transformed glial cells from death… cannabinoids-the active components of the plant Cannabis sativa.” http://www.ncbi.nlm.nih.gov/pubmed/15275820

Green Party politician Ian Driver wants a Cannabis cafe to open in Kent

“Molecular mechanisms involved in the antitumor activity of cannabinoids… Cannabinoids, the active components of Cannabis sativa, have been shown to exert antiproliferative and proapoptotic effects on a wide spectrum of tumor cells… Of interest, cannabinoids have displayed great potency in reducing the growth of glioma tumors… Cannabinoids appear to be selective antitumoral agents as they kill glioma cells without affecting the viability of non-transformed cells. Cannabinoids have been proven to inhibit glioma tumor growth… Since cannabinoids kill tumor cells without toxicity on their non transformed counterparts, they can represent a class of new potential anticancer drugs.” http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3835116/
“Antitumor effects of THC.” http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1240145/

“…cannabidiol (CBD), a non-psychoactive cannabinoid, is able to kill glioma cells, both in vivo and in vitro, independently of cannabinoid receptor stimulation… CBD exerts its antitumoral effects through modulation of the LOX pathway and of the endocannabinoid system…” http://www.ncbi.nlm.nih.gov/pubmed/18028339

“Antitumor effects of cannabidiol, a nonpsychoactive cannabinoid, on human glioma cell lines… Marijuana and its derivatives have been used in medicine for many centuries… cannabinoids (CBs) have been shown to possess antitumor properties… the nonpsychoactive CBD was able to produce a significant antitumor activity both in vitro and in vivo,” http://jpet.aspetjournals.org/content/308/3/838.long

“Cannabinoids appear to be selective antitumoral agents as they kill glioma cells without affecting the viability of nontransformed counterparts… good safety profile… remarkable antitumor effects… anticancer activity of cannabinoids.” http://www.ncbi.nlm.nih.gov/pubmed/18088200

“Marijuana Could Cure Cancer And Brain Tumors, Suggests Study” http://www.newseveryday.com/articles/13835/20150416/marijuana-fight-both-cancer-brain-tumour-research.htm

“Marijuana can kill cancer cells and even shrink brain tumours, amazing new findings reveal” http://www.mirror.co.uk/lifestyle/health/marijuana-can-kill-cancer-cells-5502082

“Cannabis extract shrinks brain tumours” http://www.newscientist.com/article/dn6283-cannabis-extract-shrinks-brain-tumours.html#.VUSoGlU4nTY

“Cannabis chemicals slows down brain cancer tumour: British Scientists” http://timesofindia.indiatimes.com/home/science/Cannabis-chemicals-slows-down-brain-cancer-tumour-British-Scientists/articleshow/45166303.cms

“Cannabis reduce tumour growth in cancer patients” http://timesofindia.indiatimes.com/home/science/Cannabis-reduce-tumour-growth-in-cancer-patients/articleshow/38456886.cms

“Cannabis can cure cancer and even shrink brain tumours” http://timesofindia.indiatimes.com/home/science/Cannabis-can-cure-cancer-and-even-shrink-brain-tumours/articleshow/46902373.cms

“Cannabinoids may cause antitumor effects by various mechanisms, including induction of cell death, inhibition of cell growth, and inhibition of tumor angiogenesis invasion and metastasis. Cannabinoids appear to kill tumor cells but do not affect their nontransformed counterparts and may even protect them from cell death.” https://medicine.yale.edu/cancer/patient/programs/sarcoma/info/info.aspx?id=CDR683767

“Study: Thinking Can Speed Up Brain Tumour Growth”
http://au.ibtimes.com/study-thinking-can-speed-brain-tumour-growth-1443392

“Cannabis Significantly Prevents Tumour Growth in Cancer Patients” http://au.ibtimes.com/cannabis-significantly-preventstumour-growth-cancer-patients-1347319

“Cannabis Extracts ‘Drastically Reduce’ Brain Tumour Size” http://www.ibtimes.co.uk/cannabis-extracts-drastically-reduce-brain-tumour-size-1475399

“Brain Tumors And Cell Phone Use Found To Be Linked (Again)” http://www.medicaldaily.com/brain-tumors-and-cell-phone-use-found-be-linked-again-310460

“Brain Tumors Removed Through The Eye Socket In Revolutionary Operation” http://www.medicaldaily.com/brain-tumors-removed-through-eye-socket-revolutionary-operation-319650

“Cannabis Shrinks Brain Tumors Associated With Highly Aggressive Form Of Cancer” http://www.medicaldaily.com/cannabis-shrinks-brain-tumors-associated-highly-aggressive-form-cancer-310720

“Towards the use of cannabinoids as antitumour agents. Various reports have shown that cannabinoids (the active components of marijuana and their derivatives) can reduce tumour growth and progression in animal models of cancer, in addition to their well-known palliative effects on some cancer-associated symptoms. This article discusses our current understanding of cannabinoids as antitumour agents” http://www.ncbi.nlm.nih.gov/pubmed/22555283

“…antitumor effects of cannabinoids in gliomas… 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

“The tumors regressed over the same period of time that cannabis was consumed via inhalation, raising the possibility that the cannabis played a role in the tumor regression.” http://www.ncbi.nlm.nih.gov/pubmed/21336992

“CB1 and CB2 expression levels have been detected in human tumors, including those of brain. Cannabinoids-endocannabinoids exert anti-inflammatory, anti-proliferative, anti-invasive, anti-metastatic and pro-apoptotic effects in different cancer types, both in vitro and in vivo animal models, after local or systemic administration. We present the available experimental and clinical data, to date, regarding the antitumor action of cannabinoids on the tumorigenesis of gliomas.”
http://www.ncbi.nlm.nih.gov/pubmed/25472761

“The efficacy of cannabinoids against high-grade glioma in animal models, mediated by two specific receptors, CB1 and CB2, raised promises for targeted treatment of the most frequent and malignant primary brain tumors… The high levels of CB2 expression would predestine those tumors to be vulnerable to cannabinoid treatment.” http://www.ncbi.nlm.nih.gov/pubmed/17239827

“Cannabinoids may cause antitumor effects by various mechanisms, including induction of cell death, inhibition of cell growth, and inhibition of tumor angiogenesis invasion and metastasis… molecular mechanisms of action of cannabinoids as antitumor agents. Cannabinoids appear to kill tumor cells but do not affect their nontransformed counterparts and may even protect them from cell death… these compounds have been shown to induce apoptosis (programmed cell death) in glioma cells in culture and induce regression of glioma tumors in mice and rats, while they protect normal glial cells…” http://www.cancer.gov/cancertopics/pdq/cam/cannabis/healthprofessional/page4

“As a therapeutic agent, most people are familiar with the palliative effects of the primary psychoactive constituent of Cannabis sativa (CS), Δ9-tetrahydrocannabinol (THC), a molecule active at both the cannabinoid 1 (CB1) and cannabinoid 2 (CB2) receptors… however, several studies have now shown that CB1 and CB2 receptor agonists can act as direct antitumor agents in a variety of aggressive cancers.” http://www.ncbi.nlm.nih.gov/pubmed/25916739

“CANNABIS can help cancer patients: Drug kills cancer cells and shrinks brain tumours, report reveals.” http://www.dailymail.co.uk/health/article-3036667/How-cannabis-help-cancer-patients-Drug-kills-cancer-cells-shrinks-brain-tumours-report-reveals.html

“Active Component In Marijuana Targets Aggressive Brain Cancer Cells… cannabinoids such as THC had anticancer effects in mice with human brain cancer cells AND PEOPLE with brain tumors.” http://www.webmd.com/cancer/brain-cancer/news/20090401/marijuana-chemical-may-fight-brain-cancer

“Cannabinoid action induces autophagy-mediated cell death through stimulation of ER stress in human glioma cells” http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2673842/

“Active Ingredient in Marijuana Inhibits Cancer Growth…the cannabinoids found in marijuana may aid in brain tumor treatment…cannabinoids inhibited genes needed for the production of vascular growth factor (VEGF) in laboratory mice with glioma brain tumors AND TWO PATIENTS with late-stage glioblastoma multiforme, a form of brain cancer.” http://www.webmd.com/cancer/news/20040815/marijuana-stall-brain-tumor-growth

“Cannabinoids Inhibit the Vascular Endothelial Growth Factor Pathway in Gliomas… Because blockade of the VEGF pathway constitutes one of the most promising antitumoral approaches currently available, the present findings provide a novel pharmacological target for cannabinoid-based therapies.” http://cancerres.aacrjournals.org/content/64/16/5617.long

“Marijuana’s Active Ingredient Targets Deadly Brain Cancer… cannabinoids could stop growth and kill cancer cells but did not harm normal cells.” http://www.webmd.com/cancer/news/20000228/marijuanas-active-ingredient-targets-deadly-brain-cancer

“Anti-tumoral action of cannabinoids: Involvement of sustained ceramide accumulation and extracellular signal-regulated kinase activation” http://www.nature.com/nm/journal/v6/n3/abs/nm0300_313.html

“Cannabinoids, the active components of Cannabis sativa L., inhibit tumor growth in laboratory animals by inducing apoptosis of tumor cells and inhibiting tumor angiogenesis. It has also been reported that cannabinoids inhibit tumor cell invasiveness… Local administration of Delta(9)-tetrahydrocannabinol (THC), the major active ingredient of cannabis, down-regulated TIMP-1 expression in mice bearing subcutaneous gliomas… THC also depressed TIMP-1 expression in cultures of various human glioma cell lines as well as in primary tumor cells obtained from a glioblastoma multiforme patient… TIMP-1 down-regulation may be a hallmark of cannabinoid-induced inhibition of glioma progression.” http://www.ncbi.nlm.nih.gov/pubmed/17675107

“Cannabinoids, the active components of Cannabis sativa L… inhibit tumor growth by inducing apoptosis of tumor cells and impairing tumor angiogenesis… these compounds inhibit tumor cell spreading… Local administration of Delta(9)-tetrahydrocannabinol (THC), the major active ingredient of cannabis, down-regulated MMP-2 expression in gliomas generated in mice… MMP-2 down-regulation constitutes a new hallmark of cannabinoid antitumoral activity.” http://www.ncbi.nlm.nih.gov/pubmed/18339876

“Cannabinoids, the active components of Cannabis sativa… Cannabinoids exert various palliative effects in cancer patients. In addition, cannabinoids inhibit the growth of different types of tumor cells, including glioma cells… Of interest, cannabinoids seem to be selective antitumoral compounds, as they kill glioma cells, but not their non-transformed astroglial counterparts.” http://www.ncbi.nlm.nih.gov/pubmed/17952650

http://www.thctotalhealthcare.com/category/brain-cancer/

The Antitumor Activity of Plant-Derived Non-Psychoactive Cannabinoids.

Posted on April 29, 2015 by David

Through the activation primarily of CB1 receptors in the central nervous system, THC can reduce nausea, emesis and pain in cancer patients undergoing chemotherapy.

During the last decade, however, several studies have now shown that CB1 and CB2 receptor agonists can act as direct antitumor agents in a variety of aggressive cancers.

In addition to THC, there are many other cannabinoids found in CS, and a majority produces little to no psychoactivity due to the inability to activate cannabinoid receptors.

For example, the second most abundant cannabinoid in CS is the non-psychoactive cannabidiol (CBD). Using animal models, CBD has been shown to inhibit the progression of many types of cancer including glioblastoma (GBM), breast, lung, prostate and colon cancer.

This review will center on mechanisms by which CBD, and other plant-derived cannabinoids inefficient at activating cannabinoid receptors, inhibit tumor cell viability, invasion, metastasis, angiogenesis, and the stem-like potential of cancer cells.

We will also discuss the ability of non-psychoactive cannabinoids to induce autophagy and apoptotic-mediated cancer cell death, and enhance the activity of first-line agents commonly used in cancer treatment.”

http://www.ncbi.nlm.nih.gov/pubmed/25916739

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

Cannabidiol stimulates Aml-1a-dependent glial differentiation and inhibits glioma stem-like cells proliferation by inducing autophagy in a TRPV2-dependent manner.

Posted on April 24, 2015 by David

“Glioma stem-like cells (GSCs) correspond to a tumor cell subpopulation, involved in glioblastoma multiforme (GBM) tumor initiation and acquired chemoresistance. Currently, drug-induced differentiation is considered as a promising approach to eradicate this tumor-driving cell population.

Recently, the effect of cannabinoids (CBs) in promoting glial differentiation and inhibiting gliomagenesis has been evidenced. Herein, we demonstrated that cannabidiol (CBD) by activating Transient Receptor Potential Vanilloid-2 (TRPV2) triggers GSCs differentiation activating the autophagic process and inhibits GSCs proliferation and clonogenic capability.

Above all, CBD and carmustine (BCNU) in combination overcome the high resistance of GSCs to BCNU treatment, by inducing apoptotic cell death…

Altogether, these results support a novel mechanism by which CBD inducing TRPV2-dependent autophagic process stimulates Aml-1a-dependent GSCs differentiation, abrogating the BCNU chemoresistance in GSCs.”

http://www.ncbi.nlm.nih.gov/pubmed/25903924

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

Reactive oxygen species-mediated therapeutic response and resistance in glioblastoma.

Posted on January 17, 2015 by David

“Glioblastoma (GBM) resistance to therapy is the most common cause of tumor recurrence, which is ultimately fatal in 90% of the patients 5 years after initial diagnosis. A sub-population of tumor cells with stem-like properties, glioma stem cells (GSCs), is specifically endowed to resist or adapt to the standard therapies, leading to therapeutic resistance.

Several anticancer agents, collectively termed redox therapeutics, act by increasing intracellular levels of reactive oxygen species (ROS).

In this study, we investigated mechanisms underlying GSC response and resistance to cannabidiol (CBD), a non-toxic, non-psychoactive cannabinoid and redox modulator.

…we demonstrated that combining CBD treatment with the inhibition of system Xc resulted in synergistic ROS increase leading to robust antitumor effects, that is, decreased GSC survival, self-renewal, and invasion.

Our investigation provides novel mechanistic insights into the antitumor activity of redox therapeutics and suggests that combinatorial approaches using small molecule modulators of ROS offer therapeutic benefits in GBM.”

http://www.ncbi.nlm.nih.gov/pubmed/25590811

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

The antitumor action of cannabinoids on glioma tumorigenesis.

Posted on December 5, 2014 by David

“Cannabinoids are a class of chemical compounds with a wide spectrum of pharmacological effects, mediated by two specific plasma membrane receptors (CB1 and CB2).

Recently, CB1 and CB2 expression levels have been detected in human tumors, including those of brain.

Cannabinoids-endocannabinoids exert anti-inflammatory, anti-proliferative, anti-invasive, anti-metastatic and pro-apoptotic effects in different cancer types, both in vitro and in vivo in animal models, after local or systemic administration.

We present the available experimental and clinical data, to date, regarding the antitumor action of cannabinoids on the tumorigenesis of gliomas.”

http://www.ncbi.nlm.nih.gov/pubmed/25472761

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

The Combination of Cannabidiol and Δ9-Tetrahydrocannabinol Enhances the Anticancer Effects of Radiation in an Orthotopic Murine Glioma Model.

Posted on November 16, 2014 by David

“High-grade glioma is one of the most aggressive cancers in adult humans and long-term survival rates are very low as standard treatments for glioma remain largely unsuccessful.

Cannabinoids have been shown to specifically inhibit glioma growth as well as neutralize oncogenic processes such as angiogenesis.

In an attempt to improve treatment outcome, we have investigated the effect of Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) both alone and in combination with radiotherapy in a number of glioma cell lines (T98G, U87MG, and GL261).

Cannabinoids were used in two forms, pure (P) and as a botanical drug substance (BDS).

Results demonstrated a duration- and dose-dependent reduction in cell viability with each cannabinoid and suggested that THC-BDS was more efficacious than THC-P, whereas, conversely, CBD-P was more efficacious than CBD-BDS.

…increase in radiosensitivity was associated with an increase in markers of autophagy and apoptosis.

These in vitro results were recapitulated in an orthotopic murine model for glioma, which showed dramatic reductions in tumor volumes when both cannabinoids were used with irradiation.

Taken together, our data highlight the possibility that these cannabinoids can prime glioma cells to respond better to ionizing radiation, and suggest a potential clinical benefit for glioma patients by using these two treatment modalities.”

http://www.ncbi.nlm.nih.gov/pubmed/25398831

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

Distinctive pattern of cannabinoid receptor type II (CB2) expression in adult and pediatric brain tumors.

Posted on March 4, 2014 by David

Unlike the abundantly expressed CB1, the CB2 receptor shows a restricted distribution in normal brain. Although brain tumors constitute the second most common malignancy in children and the prevalence of histological types of brain tumors vary significantly between the adult and pediatric populations, cannabinoid receptor expression in pediatric tumors remains unknown.

In the present study, we compared the expression of the CB2 receptor in paraffin-embedded sections from primary brain tumors of adult and pediatric patients. Most glioblastomas expressed very high levels of CB2 receptors and the expression correlated with tumor grade.

Interestingly, some benign pediatric astrocytic tumors, such as subependymal giant cell astrocytoma (SEGA), which may occasionally cause mortality owing to progressive growth, also displayed high CB2 immunoreactivity.

The high levels of CB2 expression would predestine those tumors to be vulnerable to cannabinoid treatment.

In contrast, all examined cases of embryonal tumors (medulloblastoma and S-PNET), the most frequently diagnosed malignant brain tumors in childhood, showed no or trace CB2 immunoreactivity.

Our results suggest that the CB2 receptor expression depends primarily on the histopathological origin of the brain tumor cells and differentiation state, reflecting the tumor grade.”

http://www.ncbi.nlm.nih.gov/pubmed/17239827

Endocannabinoid system in cancer cachexia.

Posted on March 1, 2014 by David

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.

Posted on March 1, 2014 by David

“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