Tag Archives: cannabinoid

Cannabinoid derivatives induce cell death in pancreatic MIA PaCa-2 cells via a receptor-independent mechanism.

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“Cannabinoids (CBs) are implicated in the control of cell survival in different types of tumors, but little is known about the role of CB system in pancreatic cancer. Herein, we investigated the in vitro antitumor activity of CBs and the potential role of their receptors in human pancreatic cancer cells MIA PaCa-2…

These findings exclude the involvement of CB receptors in the regulation of MIA PaCa-2 cell growth and put AM251 forward as a candidate for the development of novel compounds worthy to be tested in this type of neoplasia.”

http://www.ncbi.nlm.nih.gov/pubmed/16500647

Cannabinoids Halt Pancreatic Cancer, Breast Cancer Growth, Studies Say

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“Compounds in cannabis inhibit cancer cell growth in human breast cancer cell lines and in pancreatic tumor cell lines, according to a pair of preclinical trials published in the July issue of the journal of the American Association for Cancer Research.

In one trial, investigators at Complutense University in Spain and the Institut National de la Sante et de la Recherche Medicale (INSERM) in France assessed the anti-cancer activity of cannabinoids in pancreatic cancer cell lines and in animals. Cannabinoid administration selectively increased apoptosis (programmed cell death) in pancreatic tumor cells while ignoring healthy cells, researchers found. In addition, “cannabinoid treatment inhibited the spreading of pancreatic tumor cells … and reduced the growth of tumor cells” in animals.

“These findings may contribute to … a new therapeutic approach for the treatment of pancreatic cancer,” authors concluded.

In the second trial, investigators at Spain’s Complutense University reported that THC administration “reduces human breast cancer cell proliferation [in vitro] by blocking the progression of the cell cycle and by inducing apoptosis.” Authors concluded that their findings “may set the bases for a cannabinoid therapy for the management of breast cancer.”

Previous preclinical data published in May in the Journal of Pharmacological and Experimental Therapeutics reported that non-psychoactive cannabinoids, particularly cannabidiol (CBD), dramatically halt the spread of breast cancer cells and recommended their use in cancer therapy.

Separate trials have also shown cannabinoids to reduce the size and halt the spread of glioma (brain tumor) cells in animals and humans in a dose dependent manner. Additional preclinical studies have demonstrated cannabinoids to inhibit cancer cell growth and selectively trigger malignant cell death in skin cancer cells, leukemic cells, lung cancer cells, and prostate carcinoma cells, among other cancerous cell lines.”

http://norml.org/news/2006/07/06/cannabinoids-halt-pancreatic-cancer-breast-cancer-growth-studies-say

Cannabinoids Induce Apoptosis of Pancreatic Tumor Cells

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 “Pancreatic adenocarcinomas are among the most malignant forms of cancer and, therefore, it is of especial interest to set new strategies aimed at improving the prognostic of this deadly disease. The present study was undertaken to investigate the action of cannabinoids, a new family of potential antitumoral agents, in pancreatic cancer. We show that cannabinoid receptors are expressed in human pancreatic tumor cell lines …

 Cannabinoids… reduced the growth of tumor cells in two animal models of pancreatic cancer. In addition, cannabinoid treatment inhibited the spreading of pancreatic tumor cells. Moreover, cannabinoid administration selectively increased apoptosis and TRB3 expression in pancreatic tumor cells but not in normal tissue… results presented here show that cannabinoids lead to apoptosis of pancreatic tumor cells via a CB2 receptor and de novo synthesized ceramide-dependent up-regulation of p8 and the endoplasmic reticulum stress–related genes ATF-4 and TRB3.

 These findings may contribute to set the basis for a new therapeutic approach for the treatment of pancreatic cancer.

In conclusion, results presented here show that cannabinoids exert a remarkable antitumoral effect on pancreatic cancer cells in vitro and in vivo…

 These findings may help to set the basis for a new therapeutic approach for the treatment of this deadly disease.”

http://www.420magazine.com/forums/pancreatic-cancer/145013-cannabinoids-induce-apoptosis-pancreatic-tumor-cells.html

 

“Cannabinoids Induce Apoptosis of Pancreatic Tumor Cells via Endoplasmic Reticulum Stress–Related Genes“

 

Full text: http://cancerres.aacrjournals.org/content/66/13/6748.long

Regulation, function, and dysregulation of endocannabinoids in models of adipose and beta-pancreatic cells and in obesity and hyperglycemia.

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“Cannabinoid CB(1) receptor blockade decreases weight and hyperinsulinemia in obese animals and humans in a way greatly independent from food intake.

The objective of this study was to investigate the regulation and function of the endocannabinoid system in adipocytes and pancreatic beta-cells.

Endocannabinoid enzyme and adipocyte protein expression, and endocannabinoid and insulin levels were measured.

RESULTS:

Endocannabinoids are present in adipocytes with levels peaking before differentiation, and in RIN-m5F beta-cells, where they are under the negative control of insulin. Chronic treatment of adipocytes with insulin is accompanied by permanently elevated endocannabinoid signaling, whereas culturing of RIN-m5F beta-cells in high glucose transforms insulin down-regulation of endocannabinoid levels into up-regulation. Epididymal fat and pancreas from mice with diet-induced obesity contain higher endocannabinoid levels than lean mice. Patients with obesity or hyperglycemia caused by type 2 diabetes exhibit higher concentrations of endocannabinoids in visceral fat or serum, respectively, than the corresponding controls. CB(1) receptor stimulation increases lipid droplets and decreases adiponectin expression in adipocytes, and it increases intracellular calcium and insulin release in RIN-m5F beta-cells kept in high glucose.

CONCLUSIONS:

Peripheral endocannabinoid overactivity might explain why CB(1) blockers cause weight-loss independent reduction of lipogenesis, of hypoadiponectinemia, and of hyperinsulinemia in obese animals and humans.”

http://jcem.endojournals.org/content/91/8/3171.long

Mechanisms for the coupling of cannabinoid receptors to intracellular calcium mobilization in rat insulinoma beta-cells.

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“In RIN m5F rat insulinoma beta-cells, agonists at cannabinoid CB(1) receptors modulate insulin release. Here we investigated in these cells the effect of the activation of cannabinoid CB(1) and CB(2) receptors on intracellular Ca(2+) ([Ca(2+)](i)). The CB(1) agonist arachidonoyl-chloro-ethanolamide (ACEA), and the CB(2) agonist JWH133, elevated [Ca(2+)](i) in a way sensitive to the inhibitor of phosphoinositide-specific phospholipase C (PI-PLC), U73122 (but not to pertussis toxin and forskolin), and independently from extracellular Ca(2+). PI-PLC-dependent Ca(2+) mobilization by ACEA was entirely accounted for by activation of inositol-1,3,4-phosphate (IP(3)) receptors on the endoplasmic reticulum (ER), whereas the effect of JWH133 was not sensitive to all tested inhibitors of IP(3) and ryanodine receptors. ACEA, but not JWH133, significantly inhibited the effect on [Ca(2+)](i) of bombesin, which acts via G(q/11)- and PI-PLC-coupled receptors in insulinoma cells. The endogenous CB(1) agonists, anandamide and N-arachidonoyldopamine, which also activate transient receptor potential vanilloid type 1 (TRPV1) receptors expressed in RIN m5F cells, elevated [Ca(2+)](i) in the presence of extracellular Ca(2+) in a way sensitive to both CB(1) and TRPV1 antagonists. These results suggest that, in RIN m5F cells, CB(1) receptors are coupled to PI-PLC-mediated mobilization of [Ca(2+)](i) and might inhibit bombesin signaling.”

http://www.ncbi.nlm.nih.gov/pubmed/17585904

Effects of CP 55,940–agonist of CB1 cannabinoid receptors on ghrelin and somatostatin producing cells in the rat pancreas.

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“Cannabinoids participate in the modulation of numerous functions in the human organism, increasing the sense of hunger, affecting carbohydrate and lipid metabolism, and controlling systemic energy balance mechanisms. Moreover, they influence the endocrine system functions, acting via two types of receptors, CB1 and CB2. The aim of the present study was to examine the number, distribution and activity of ghrelin and somatostatin producing endocrine cells in the pancreas of rats after a single administration of selective CP 55,940 agonist of CB1 receptor. The study was performed on 20 rats. Neuroendocrine cells were identified by immunohistochemical reactions, involving specific antibodies against ghrelin and somatostatin. The distribution and number of ghrelin- and somatostatin-immunoreactive cells were separately studied in five pancreas islets of each section. A performed analysis showed a decreased number of somatostatin-immunoreactive cells and a weak immunoreactivity of ghrelin and somatostatin containing neuroendocrine cells in the pancreatic islets of experimental rats, compared to control animals. The obtained results suggest that a single administration of a selective CP 55,940 agonist of CB1 receptor influences the immunoreactivity of endocrine cells with ghrelin and somatostatin expression in the pancreas islets.”

http://www.ncbi.nlm.nih.gov/pubmed/22532145

The endocannabinoid system in the regulation of emotions throughout lifespan: a discussion on therapeutic perspectives.

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“Alterations in emotion regulation processes may form the basis of psychopathologies. The endocannabinoid (eCB) system, composed of endogenous ligands, the enzymatic machinery in charge of their metabolism and the specific metabotropic receptors, has emerged as a major neuromodulatory system critically involved in the control of emotional homeostasis and stress responsiveness. Data from animal models indicate that the eCB system plays a key role in brain development, and is probably involved in the control of emotional states from early developmental stages.

The present review summarizes the latest information on the role of the eCB system in emotionality and anxiety-related disorders throughout the lifespan. Putative therapeutic strategies based on the pharmacological modulation of this system will be discussed.

 Given the fact that the pharmacological modulation of the eCB system has recently arisen as a promising strategy in the management of anxiety and mood disorders, the potential efficacy of this pharmacological approach (i.e. blockers of the catabolic pathway) will be discussed, as well as pharmacological alternatives such as modulators of cannabinoid receptors other than the classical CB1 receptor, or administration of other plant-derived compounds (e.g. cannabidiol).”

http://www.ncbi.nlm.nih.gov/pubmed/21693551

Role of endocannabinoid system in the ventral hippocampus of rats in the modulation of anxiety-like behaviours.

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“The effects of unilateral intra-ventral hippocampus injection of URB597, a fatty acid amid hydrolase inhibitor, and AM251, a selective CB(1) receptor antagonist, on anxiety-related behaviours using elevated plus-maze test of anxiety were evaluated in the present study. Possible involvement of GABAergic system in those effects of URB597 was also evaluated. Injection of URB597 at the doses of 0.01, 0.1 and 1 microg/rat showed significant anxiogenic-like effects at 0.1 and 1 microg/rat. However, intra-ventral hippocampus injection of AM251 at the doses of 0.001, 0.01 and 0.1 microg/rat did not produce any significant effect in the elevated plus-maze. The ineffective doses of selective GABA(A) receptor antagonist, bicuculline (2 microg/rat) and selective GABA(B) receptor antagonist, phaclofen (1 microg/rat) on anxiety-related behaviours were also injected with URB597 (0.1 microg/rat). The present data showed that neither bicuculline nor phaclofen affected the anxiogenic-like effects of URB597. The results showed that injection of URB597 into the ventral hippocampus may be anxiogenic and GABAergic system may not be involved in its anxiogenic-like effects.”

http://www.ncbi.nlm.nih.gov/pubmed/19614892

An Endocannabinoid Signaling System Modulates Anxiety-like Behavior in Male Syrian Hamsters

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“An endocannabinoid signaling system has not been identified in hamsters.

We examined the existence of an endocannabinioid signaling system in Syrian hamsters using neuroanatomical, biochemical and behavioral pharmacological approaches.

The distribution of cannabinoid receptors was mapped and membrane fatty-acid amide hydrolase (FAAH) activity and levels of fatty-acid amides were measured in hamster brain. The impact of cannabinoid CB1 receptor blockade and inhibition of FAAH was evaluated in the elevated plus maze, rota-rod test and models of unconditioned and conditioned social defeat.

Results

A characteristic heterogeneous distribution of cannabinoid receptors was detected in hamster brain..

Endocannabinoids engage functional CB1 receptors in hamster brain to suppress anxiety-like behavior and undergo enzymatic hydrolysis catalyzed by FAAH. Our results further suggest that neither unconditioned nor conditioned social defeat in the Syrian hamster is dependent upon cannabinoid CB1 receptor activation.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2694060/

The endocannabinoid nervous system: unique opportunities for therapeutic intervention.

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“The active principle in marijuana, Delta(9)-tetrahydrocannabinol (THC), has been shown to have wide therapeutic application for a number of important medical conditions, including pain, anxiety, glaucoma, nausea, emesis, muscle spasms, and wasting diseases. Delta(9)-THC binds to and activates two known cannabinoid receptors found in mammalian tissue, CB1 and CB2. The development of cannabinoid-based therapeutics has focused predominantly on the CB1 receptor, based on its predominant and abundant localization in the CNS.

Like most of the known cannabinoid agonists, Delta(9)-THC is lipophilic and relatively nonselective for both receptor subtypes.

Clinical studies show that nonselective cannabinoid agonists are relatively safe and provide therapeutic efficacy, but that they also induce psychotropic side effects. Recent studies of the biosynthesis, release, transport, and disposition of anandamide are beginning to provide an understanding of the role of lipid transmitters in the CNS. This review attempts to link current understanding of the basic biology of the endocannabinoid nervous system to novel opportunities for therapeutic intervention.

This new knowledge may facilitate the development of cannabinoid receptor-targeted therapeutics with improved safety and efficacy profiles.”

http://www.ncbi.nlm.nih.gov/pubmed/11448725