[Cannabinoid WIN55, 212-2 inhibits proliferation, invasion and migration of human SMMC-7721 hepatocellular carcinoma cells].

Posted on April 30, 2016 by David

“Objective To investigate the effects of WIN55, 212-2 (WIN) on the proliferation, invasion and migration of SMMC-7721 hepatocellular carcinoma cells and its underlying mechanisms. Methods SMMC-7721 cells were treated with (0, 1, 5, 10, 20) μmol/L WIN, and cell viability was determined by CCK-8 assay. The morphological changes of the cells were observed under a fluorescence microscope with Hoechst33258 staining. Cell apoptosis was measured by flow cytometry combined with annexin V-FITC/PI staining. The expression levels of apoptosis-related proteins P53, P21, Bcl-2 and Bax, and the phosphorylated AKT (p-AKT) and phosphorylated extracellular signal-regulated kinase (p-ERK) were analyzed by Western blotting. Transwell(TM) invasion assay was used to detect cell invasion ability. Would healing assay was performed to test cell migration ability. The expression level of matrix metalloproteinase 14 (MMP-14) was evaluated by Western blotting. Results WIN inhibited the proliferation of SMMC-7721 cells and induced cell apoptosis in a dose-dependent manner. After treatment with WIN, the cell nucleus concentrated and broken, indicating obvious cell apoptosis. Western blotting exhibited an up-regulation in the protein expression of P53, P21 and Bax. And the anti-apoptotic protein Bcl-2 was repressed. The expression levels of AKT, p-AKT and p-ERK were down-regulated, whereas the expression of total ERK was not obviously changed. Compared with control group, there was a significant inhibition of cell invasion and migration abilities when SMMC-7721 cells were treated with WIN. The expression level of MMP-14 decreased as well. Conclusion WIN can inhibit the proliferation of SMMC-7721 cells and induce cell apoptosis. The mechanism is associated with the activation of P53 and the inhibition of AKT, p-AKT and p-ERK. WIN can inhibit the invasion and migration of SMMC-7721 cells through down-regulating the protein expression of MMP-14.”

http://www.ncbi.nlm.nih.gov/pubmed/27126940

Dronabinol has preferential antileukemic activity in acute lymphoblastic and myeloid leukemia with lymphoid differentiation patterns

Posted on January 19, 2016 by David

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“It has been previously demonstrated in several cancer models, that Dronabinol (THC) may have anti-tumor activity – however, controversial data exists for acute leukemia. We have anecdotal evidence that THC may have contributed to disease control in a patient with acute undifferentiated leukemia.

To test this hypothesis, we evaluated the antileukemic efficacy of THC in several leukemia cell lines and native leukemia blasts cultured ex vivo.

We here reveal a novel aspect of dronabinol, a cannabinoid derivative, which displays remarkable antiproliferative as well as proapoptotic efficacy in a distinct leukemia patient cohort – in vitro and in ex vivo native leukemia blasts. It has been previously reported that cannabinoids display anticancer properties. However, due to legal issues the use and exploration of such agents is highly limited in many countries.

Importantly, we demonstrate that antileukemic concentrations are achievable in vivo.

Our study provides rigorous data to support clinical evaluation of THC as a low-toxic therapy option in a well defined subset of acute leukemia patients.”

http://www.ncbi.nlm.nih.gov/pubmed/26775260

http://bmccancer.biomedcentral.com/articles/10.1186/s12885-015-2029-8

Anti Proliferative and Pro Apoptotic Effects of Flavonoid Quercetin Are Mediated by CB1 Receptor in Human Colon Cancer Cell Lines.

Posted on January 5, 2016 by David

“Quercetin, the major constituent of flavonoid and widely present in fruits and vegetables, is an attractive compound for cancer prevention due to its beneficial anti proliferative effects, showing a crucial role in the regulation of apoptosis and cell cycle signaling.

In vitro studies have demonstrated that quercetin specifically influences colon cancer cell proliferation.

Our experiments, using human colon adenocarcinoma cells, confirmed the anti proliferative effect of quercetin and gave intriguing new insight in to the knowledge of the mechanisms involved…

These findings open new perspectives for anticancer therapeutic strategies.”

http://www.ncbi.nlm.nih.gov/pubmed/25893829

“Flavonoid glycosides and cannabinoids from the pollen of Cannabis sativa L.” http://www.ncbi.nlm.nih.gov/pubmed/15688956

Endocannabinoids and Cancer.

Posted on September 27, 2015 by David

“A large body of evidence shows that cannabinoids, in addition to their well-known palliative effects on some cancer-associated symptoms, can reduce tumour growth in animal models of cancer.

They do so by modulating key cell signalling pathways involved in the control of cancer cell proliferation and survival.

In addition, cannabinoids inhibit angiogenesis and cell proliferation in different types of tumours in laboratory animals.

By contrast, little is known about the biological role of the endocannabinoid system in cancer physio-pathology, and several studies suggest that it may be over-activated in cancer.

In this review, we discuss our current understanding of cannabinoids as antitumour agents, focusing on recent advances in the molecular mechanisms of action, including resistance mechanisms and opportunities for combination therapy approaches.”

http://www.ncbi.nlm.nih.gov/pubmed/26408171

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

Anandamide exerts its antiproliferative actions on cholangiocarcinoma by activation of the GPR55 receptor

Posted on July 13, 2015 by David

“We have previously shown that AEA exerts growth-suppressing effects on cholangiocarcinoma by inducing apoptosis.

At the time, we assumed that AEA was acting via a receptor-independent mechanism.

However, given the recent discovery and characterization of GPR55 as a novel AEA receptor, our data need to be reassessed to determine if GPR55 activation can decrease cholangiocarcinoma cell proliferation.

Thus, our aims are to determine if these AEA-mediated effects on cholangiocarcinoma cell growth can be attributed to the activation of GPR55.

This data represent the first evidence that GPR55 activation by anandamide can lead to the recruitment and activation of the Fas death receptor complex and that targeting GPR55 activation may be a viable option for the development of therapeutic strategies to treat cholangiocarcinoma.

In conclusion, we have clearly demonstrated a role for GPR55 in the antiproliferative effects of AEA in vivo andin vitro…

Cholangiocarcinoma has a very poor prognosis and survival rate; therefore we propose that the development of novel therapeutic strategies that target GPR55 may prove beneficial for the treatment of this devastating disease.

Consistent with our observation that AEA has antiproliferative and pro-apoptotic properties, cannabinoids of various origins (endogenous, plant-derived or synthetic analogues) have been shown to suppress cancer cell growth in vitro as well as in vivo.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3126905/

The endocannabinoid anandamide inhibits cholangiocarcinoma growth via activation of the noncanonical Wnt signaling pathway.

Posted on July 13, 2015 by David

“Cholangiocarcinomas are cancers that have poor prognosis and limited treatment options.

Marijuana and its derivatives have been used in medicine for many centuries.

…cannabinoids might be effective antitumoral agents because of their ability to inhibit the growth of various types of cancer cell lines in culture and in laboratory animals.

Indeed, we have recently demonstrated that the endocannabinoid anandamide (AEA) has antiproliferative effects on cholangiocarcinoma cell lines in vitro via a cannabinoid receptor-independent pathway involving the stabilization of lipid raft-membrane structures and the recruitment of death-receptor complexes into the lipid rafts.

Modulation of the endocannabinoid system may be important in cholangiocarcinoma treatment.

The antiproliferative actions of the noncanonical Wnt signaling pathway warrants further investigation to dissect the mechanism by which this may occur.

We propose that the development of novel therapeutic strategies aimed at modulating the endocannabinoid system, or mimicking the mode of action of AEA, would prove beneficial for the treatment of this devastating disease.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2604798/

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/

Engineering of Δ9-tetrahydrocannabinol delivery systems based on surface modified-PLGA nanoplatforms.

Posted on September 30, 2014 by David

“The objective of this work is to develop a nanoplatform that can potentiate the oral administration of Δ9-tetrahidrocannabinol, a highly lipophilic active agent with very promising antiproliferative and antiemetic activities…

Results were satisfactorily used to define the optimum engineering conditions to formulate surface modified nanoparticles for the efficient oral administration of Δ9-tetrahydrocannabinol.

To the best of our knowledge, this is the first time that biocompatible polymeric nanoparticles have been formulated for Δ9-tetrahydrocannabinol delivery.”

http://www.ncbi.nlm.nih.gov/pubmed/25262411

CBD-Rich Marijuana Fights Colon Cancer, New Study Finds

Posted on June 4, 2014 by David

“In 2008, over one million individuals were diagnosed with colon cancer, also known as colorectal cancer or bowel cancer and it caused over 600,000 deaths globally. The results of a study published in the journal Phytomedicine in October 2013 suggest that a botanical extract made from high-CBD (cannabidiol) cannabis can selectively target colon cancer cells, while leaving healthy cells unharmed.

Researchers were able to reduce tumor growth and pre-cancerous lesions in mice with colon cancer using the pot molecule CBD as part of a “botanical drug substance”. The authors believe that CBD’s benefits as demonstrated by the results of the study could have clinical relevance for the use of cannabis-based medicines in cancer patients.

Current colon cancer treatments are not only very toxic but also fail to prevent the progression of the disease in some patients. Disease incidence and mortality have not reduced using screening strategies for colon cancer.

Researchers have made progress in investigating cannabis as a treatment for breast and brain cancers considering its antiproliferative CB1 and CB2-mediated effects in colorectal cancer cells and action in experimental models of colon cancer. The study was partially funded through grants from GW Pharmaceuticals and lead by researchers from Italy and the UK.”

http://blog.sfgate.com/smellthetruth/2014/01/06/cbd-rich-marijuana-fights-colon-cancer-new-study-finds/

“Inhibition of colon carcinogenesis by a standardized Cannabis sativa extract with high content of cannabidiol” http://www.ncbi.nlm.nih.gov/pubmed/24373545

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

Physiological intestinal oxygen modulates the Caco-2 cell model and increases sensitivity to the phytocannabinoid cannabidiol.

Posted on January 28, 2014 by David

“The Caco-2 cell model is widely used as a model of colon cancer… these cells were more sensitive to cannabidiol-induced antiproliferative actions through changes in cellular energetics…

These effects could impact on its development as an anticancer therapeutic…”

http://www.ncbi.nlm.nih.gov/pubmed/24464350