Cannabisin B induces autophagic cell death by inhibiting the AKT/mTOR pathway and S phase cell cycle arrest in HepG2 cells.

Posted on June 2, 2015 by David

“This study investigates the anticancer properties of cannabisin B, purified from hempseed hull, in HepG2 human hepatoblastoma cells.

The results indicate that cannabisin B significantly inhibited cell proliferation by inducing autophagic cell death rather than typical apoptosis.

Cell viability transiently increased upon the addition of a low concentration of cannabisin B but decreased upon the addition of high concentrations.

Cannabisin B-induced changes in cell viability were completely inhibited by pre-treatment with 3-methyladenine (3-MA), indicating that the induction of autophagy by cannabisin B caused cell death.

Additionally, cannabisin B induced S phase cell cycle arrest in a dose-dependent manner.

Moreover, cannabisin B was found to inhibit survival signaling by blocking the activation of AKT and down-stream targets of the mammalian target of rapamycin (mTOR).

These findings suggest that cannabisin B possesses considerable antiproliferative activity and that it may be utilised as a promising chemopreventive agent against hepatoblastoma disease.”

http://www.ncbi.nlm.nih.gov/pubmed/23411211

http://www.thctotalhealthcare.com/category/liver-cancer-2/

Cannabinoid signaling and liver therapeutics.

Posted on February 19, 2015 by David

Journal of Hepatology Home

“Over the last decade, the endocannabinoid system has emerged as a pivotal mediator of acute and chronic liver injury, with the description of the role of CB1 and CB2 receptors and their endogenous lipidic ligands in various aspects of liver pathophysiology.

A large number of studies have demonstrated that CB1 receptor antagonists represent an important therapeutic target, owing to beneficial effects on lipid metabolism and in light of its antifibrogenic properties.

Unfortunately, the brain-penetrant CB1 antagonist rimonabant, initially approved for the management of overweight and related cardiometabolic risks, was withdrawn because of an alarming rate of mood adverse effects.

However, the efficacy of peripherally-restricted CB1 antagonists with limited brain penetrance has now been validated in preclinical models of NAFLD, and beneficial effects on fibrosis and its complications are anticipated.

CB2 receptor is currently considered as a promising anti-inflammatory and antifibrogenic target, although clinical development of CB2 agonists is still awaited.

In this review, we highlight the latest advances on the impact of the endocannabinoid system on the key steps of chronic liver disease progression and discuss the therapeutic potential of molecules targeting cannabinoid receptors…

Overwhelming evidence supports the therapeutic potential of peripherally-restricted CB1 antagonists and CB2 agonists in the management of chronic liver diseases.”

http://www.journal-of-hepatology.eu/article/S0168-8278(13)00212-2/fulltext

http://www.thctotalhealthcare.com/category/liver-disease/

Emerging role of cannabinoids in gastrointestinal and liver diseases: basic and clinical aspects.

Posted on February 19, 2015 by David

“A multitude of physiological effects and putative pathophysiological roles have been proposed for the endogenous cannabinoid system in the gastrointestinal tract, liver and pancreas.

These range from effects on epithelial growth and regeneration, immune function, motor function, appetite control, fibrogenesis and secretion.

Cannabinoids have the potential for therapeutic application in gut and liver diseases.

Two exciting therapeutic applications in the area of reversing hepatic fibrosis as well as antineoplastic effects may have a significant impact in these diseases.

This review critically appraises the experimental and clinical evidence supporting the clinical application of cannabinoid receptor-based drugs in gastrointestinal, liver and pancreatic diseases.

Application of modern pharmacological principles will most probably expand the selective modulation of the cannabinoid system peripherally in humans.

We anticipate that, in addition to the approval in several countries of the CB(1) antagonist, rimonabant, for the treatment of obesity and associated metabolic dysfunctions, other cannabinoid modulators are likely to have an impact on human disease in the future, including hepatic fibrosis and neoplasia.”

http://www.ncbi.nlm.nih.gov/pubmed/18397936

http://www.thctotalhealthcare.com/category/liver-disease/

Beneficial paracrine effects of cannabinoid receptor 2 on liver injury and regeneration.

Posted on February 19, 2015 by David

“Accumulating data indicate that the cannabinoid system is a crucial mediator in the pathogenesis of a variety of liver diseases.

In the present study we show that CB2 receptors reduce liver injury and accelerate liver regeneration via distinct pathways.

CB2 receptors reduce liver injury and promote liver regeneration following acute insult, via distinct paracrine mechanisms involving hepatic myofibroblasts.

These results suggest that CB2 agonists display potent hepatoprotective properties, in addition to their antifibrogenic effects.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3246453/
“Association of the cannabinoid receptor 2 (CB2) Gln63Arg polymorphism with indices of liver damage in obese children: an alternative way to highlight the CB2 hepatoprotective properties.” http://www.ncbi.nlm.nih.gov/pubmed/21608006

http://www.thctotalhealthcare.com/category/liver-disease/

Anandamide Drives Cell Cycle Progression through CB1 Receptors in a Rat Model of Synchronized Liver Regeneration.

Posted on February 18, 2015 by David

“The endocannabinoid system, through cannabinoid receptor signaling by endocannabinoids, is involved in a wide range of functions and physiopathological conditions.

… liver regeneration, a useful in vivo model of synchronized cell proliferation, is characterized by a peak of anandamide that elicits through CB1 receptor the expression of critical mitosis genes. The aim of this study was to focus on the timing of endocannabinoid signaling changes during the different phases of the cell cycle, exploiting the rat liver regeneration model following partial hepatectomy…

These results support the notion that the signaling mediated by anandamide through CB1 receptor may be important for the entry and progression of cells into the cell cycle and hence for their proliferation under mitogenic signals.”

http://www.ncbi.nlm.nih.gov/pubmed/25684344

http://www.thctotalhealthcare.com/category/liver-disease/

Protective and therapeutic effects of cannabis plant extract on liver cancer induced by dimethylnitrosamine in mice

Posted on February 17, 2015 by David

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“Hepatocellular carcinomas will emerge as a major form of malignancy in the coming decades.

When these tumors are in advanced stages, few therapeutic options are available.

Therefore, it is essential to search for new treatment modalities to fight this disease.

Aim

Evaluate the possible protective and therapeutic effects of Cannabis extract on dimethylnitrosamine (DMNA)-induced hepatocarcinogenicity in mice.

Conclusion

The protective effect of cannabis extract is more pronounced in group taking cannabis before DMNA.

Cannabinoids might exert their anti-tumor effects by the direct induction of apoptosis and can decrease telomerase activity by inhibiting the expression of the TERT gene…”

http://www.sciencedirect.com/science/article/pii/S209050681400027X

http://www.thctotalhealthcare.com/category/liver-cancer-2/

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

Upregulated expression of CAP1 is associated with tumor migration and metastasis in hepatocellular carcinoma.

Posted on February 27, 2014 by David

“Hepatocellular carcinoma (HCC) is one of the most common cancers that exhibits high incidences of intrahepatic metastasis and tumor recurrence.

Adenylate cyclase-associated protein 1 (CAP1)… was recently reported to play a role in cell motility and the pathology of pancreatic cancer. In this study, we examined a potential role of CAP1 in HCC progression, and found that CAP1 was overexpressed in HCC specimens…

Collectively, our results indicated that upregulated expression of CAP1 might contribute heavily to the metastasis of HCC.”

http://www.ncbi.nlm.nih.gov/pubmed/24359721

http://www.thctotalhealthcare.com/category/hepatocellular-carcinoma-hcc/

Inhibition of adenylate cyclase by delta 9-tetrahydrocannabinol in mouse spleen cells: a potential mechanism for cannabinoid-mediated immunosuppression.

Posted on February 27, 2014 by David

“The ability of delta 9-Tetrahydrocannabinol (delta 9-THC) to modulate adenylate cyclase activity in mouse spleen cells was investigated…

delta 9-THC treated spleen cells demonstrated a 33% inhibition and a 66% inhibition in intracellular cAMP… respectively…

These studies suggest that inhibition of immune function by delta 9-THC may be mediated through the inhibition of intracellular cAMP early after antigen stimulation.”

http://www.ncbi.nlm.nih.gov/pubmed/1321935