Marijuana Study Shows Brain Cancer Cells Eat Themselves

“… a study released by researchers at the Complutense University in Madrid describes how marijuana’s active chemical, tetrahydrocannabinol, can aid anti-cancer therapies due to its ability to coax cancerous brain cells to self-digest.

The research involved stimulating cancer growth in mice and then injecting sites near the tumors with THC every day. An experimental trial involving two brain cancer patients were also analyzed by the researchers.

It studied how an aggressive brain tumor type was affected by THC, noting that the findings fell in line with the tests done on mice. They say the work shows how “a new family of potential antitumoral agent” exists among THC and related cannabinoids.”

http://www.shortnews.com/start.cfm?id=78020

“Cannabinoid action induces autophagy-mediated cell death through stimulation of ER stress in human glioma cells”

Full Text: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2673842/

Involvement of PPARγ in the antitumoral action of cannabinoids on hepatocellular carcinoma.

Logo of cddis “Cannabinoids exert antiproliferative effects in a wide range of tumoral cells, including hepatocellular carcinoma (HCC) cells. In this study, we examined whether the PPARγ-activated pathway contributed to the antitumor effect of two cannabinoids, Δ9-tetrahydrocannabinol (THC) and JWH-015, against HepG2 and HUH-7 HCC cells. Taken together, we demonstrate for the first time that the antiproliferative action of the cannabinoids THC and JWH-015 on HCC, in vitro and in vivo, are modulated by upregulation of PPARγ-dependent pathways.”  http://www.ncbi.nlm.nih.gov/pubmed/23640460

“The antitumor activity of cannabinoids against HCC cells has been related to the ability of these drugs to induce apoptosis and autophagy. In particular, it has been previously described that cannabinoids arrest cell proliferation, reduce cell migration and inhibit angiogenesis, and therefore, cannabinoid-like compounds offer a therapeutic potential for the treatment of many types of cancer.”  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3674350/

“We here illustrate that the cannabinoids THC and JWH-015 exert antitumor effect against the human HCC cell lines HepG2 and HUH-7 in vitro and in vivo through PPARγ.”  https://www.nature.com/articles/cddis2013141

Evaluation of anti-invasion effect of cannabinoids on human hepatocarcinoma cells.

“Cancer is a disease characterized by abnormal growth of cells. One of the most common types of liver cancers is called hepatocellular carcinoma (HCC) which is highly metastatic. As most of cannabinoids have shown anticancer effect against different cell lines in a number of reports, a biological investigation of two cannabinoids, CB65 (CB2 receptor agonist) and ACEA (CB1 receptor agonist) was carried out in this study.

In an attempt to find natural products as a new solution of cancer, this study was designed to investigate the potential antitumoral and anti-invasive activity of cannabinoids…

The results revealed that both cannabinoids reduce cell viability, cell invasion as well as MMP-2 and MMP-9 expression in higher dose of 20 nM. Furthermore, higher concentrations of examined cannabinoids were more effective.

These data suggest ACEA and CB65 as an option for novel treatment of hepatocellular cancer.

Our findings may contribute to design of new therapeutic strategies for the management of HCC.”

http://www.ncbi.nlm.nih.gov/pubmed/22978792

Cannabinoid receptors as novel targets for the treatment of melanoma

“Melanoma causes the greatest number of skin cancer-related deaths worldwide. Here, we evaluated the efficacy of cannabinoid receptor agonists, a new family of potential antitumoral compounds, at skin melanoma. Human melanomas and melanoma cell lines express CB1 and CB2 cannabinoid receptors. Activation of these receptors decreased growth, proliferation, angiogenesis and metastasis, and increased apoptosis, of melanomas in mice. Cannabinoid antimelanoma activity was independent of the immune status of the animal, could be achieved without overt psychoactive effects and was selective for melanoma cells vs. normal melanocytes.

Cannabinoid antiproliferative action on melanoma cells…

 These findings may contribute to the design of new chemotherapeutic strategies for the management of melanoma.

 …the present report, together with the implication of CB2 receptors in the control of processes such as pain initiation, emesis, and inflammation, opens the attractive possibility of finding cannabinoid-based therapeutic strategies devoid of nondesired psychotropic side effects.

Specifically, the antiproliferative effect of cannabinoids reported here may set the basis for a new therapeutic approach for the treatment of malignant melanoma.”

Full text: http://www.fasebj.org/content/20/14/2633.long

Inhibition of skin tumor growth and angiogenesis in vivo by activation of cannabinoid receptors

“Cannabinoids inhibit skin tumor growth in vivo. Here we show that the CB1 and the CB2 receptor are expressed in normal skin and skin tumors of mice and humans. In cell culture experiments pharmacological activation of cannabinoid receptors induced the apoptotic death of tumorigenic epidermal cells, whereas the viability of nontransformed epidermal cells remained unaffected. Local administration of the mixed CB1/CB2 agonist WIN-55,212-2 or the selective CB2 agonist JWH-133 induced a considerable growth inhibition of malignant tumors generated by inoculation of epidermal tumor cells into nude mice. Cannabinoid-treated tumors showed an increased number of apoptotic cells.

 

Cannabinoids, the active components of Cannabis sativa linnaeus (marijuana)…

Marijuana and its derivatives have been used in medicine for many centuries, and currently there is a renaissance in the study of the therapeutic effects of cannabinoids… cannabinoids may be potential antitumoral agents owing to their ability to induce the regression of various types of tumors, including lung adenocarcinoma, glioma, and thyroid epithelioma in animal models.

This background prompted us to explore whether (a) the skin and skin tumors express cannabinoid receptors; (b) cannabinoid receptor activation exerts a growth-inhibiting action on skin tumors in vivo; and (c) inhibition of angiogenesis is implicated in the anti-tumoral effect of cannabinoids.

Our data show that (a) CB1 and CB2 receptors are present in the skin and skin tumors; (b) local cannabinoid receptor activation induces the regression of skin tumors in vivo; and (c) at least two mechanisms may be involved in this action: direct apoptosis of tumor cells and inhibition of tumor angiogenesis.

These results support a new therapeutic approach for the treatment of skin tumors.”

Full text: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC151833/

Cannabinoids Induce Apoptosis of Pancreatic Tumor Cells

 “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

Cannabinoid signaling in glioma cells

“Significant alterations of a balance in the cannabinoid system between the levels of endogenous ligands and their receptors occur during malignant transformation in various types of cancer, including gliomas. Cannabinoids exert anti-proliferative action in tumor cells. Induction of cell death by cannabinoid treatment…”

 http://www.ncbi.nlm.nih.gov/pubmed/22879071

Cannabinoids and gliomas.

Abstract

“Cannabinoids, the active components of Cannabis sativa L., act in the body by mimicking endogenous substances–the endocannabinoids–that activate specific cell surface receptors. Cannabinoids exert various palliative effects in cancer patients. In addition, cannabinoids inhibit the growth of different types of tumor cells, including glioma cells, in laboratory animals. They do so by modulating key cell signaling pathways, mostly the endoplasmic reticulum stress response, thereby inducing antitumoral actions such as the apoptotic death of tumor cells and the inhibition of tumor angiogenesis. Of interest, cannabinoids seem to be selective antitumoral compounds, as they kill glioma cells, but not their non-transformed astroglial counterparts. On the basis of these preclinical findings, a pilot clinical study of Delta(9)-tetrahydrocannabinol (THC) in patients with recurrent glioblastoma multiforme has been recently run. The good safety profile of THC, together with its possible growth-inhibiting action on tumor cells, justifies the setting up of future trials aimed at evaluating the potential antitumoral activity of cannabinoids.”

http://www.ncbi.nlm.nih.gov/pubmed/17952650

Delta 9-tetrahydrocannabinol inhibits cell cycle progression by downregulation of E2F1 in human glioblastoma multiforme cells.

“The active components of Cannabis sativa L., Cannabinoids, traditionally used in the field of cancer for alleviation of pain, nausea, wasting and improvement of well-being have received renewed interest in recent years due to their diverse pharmacologic activities such as cell growth inhibition, anti-inflammatory activity and induction of tumor regression. Here we used several experimental approaches, which identified delta-9-tetrahydrocannabinol (Delta(9)-THC) as an essential mediator of cannabinoid antitumoral action.”

“CONCLUSIONS:

Delta(9)-THC is shown to significantly affect viability of GBM cells via a mechanism that appears to elicit G(1) arrest due to downregulation of E2F1 and Cyclin A. Hence, it is suggested that Delta(9)-THC and other cannabinoids be implemented in future clinical evaluation as a therapeutic modality for brain tumors.”

http://www.ncbi.nlm.nih.gov/pubmed/17934890

Cannabinoids Inhibit the Vascular Endothelial Growth Factor Pathway in Gliomas

“Cannabinoids, the active components of Cannabis sativa L. (marijuana), and their derivatives exert a wide array of effects by activating their specific G protein-coupled receptors CB1 and CB2, which are normally engaged by a family of endogenous ligands–the endocannabinoids. Marijuana and its derivatives have been used in medicine for many centuries, and there is currently a renaissance in the study of the therapeutic effects of cannabinoids. Today, cannabinoids are approved to palliate the wasting and emesis associated with cancer and AIDS chemotherapy, and ongoing clinical trials are determining whether cannabinoids are effective agents in the treatment of pain, neurodegenerative disorders such as multiple sclerosis, and traumatic brain injury . In addition, cannabinoid administration to mice and/or rats induces the regression of lung adenocarcinomas, gliomas, thyroid epitheliomas, lymphomas, and skin carcinomas. These studies have also evidenced that cannabinoids display a fair drug safety profile and do not produce the generalized cytotoxic effects of conventional chemotherapies, making them potential antitumoral agents.” 

“Gliomas are one of the most malignant forms of cancer, resulting in the death of affected patients within 1–2 two years after diagnosis. Current therapies for glioma treatment are usually ineffective or just palliative. Therefore, it is essential to develop new therapeutic strategies for the management of glioblastoma multiforme, which will most likely require a combination of therapies to obtain significant clinical results. In line with the idea that anti-VEGF treatments constitute one of the most promising antitumoral approaches currently available, the present laboratory and clinical findings provide a novel pharmacological target for cannabinoid-based therapies.”

“The use of cannabinoids in medicine is limited by their psychoactive effects mediated by neuronal CB1 receptors. Although these adverse effects are within the range of those accepted for other medications, especially in cancer treatment, and tend to disappear with tolerance on continuous use, it is obvious that cannabinoid-based therapies devoid of side-effects would be desirable. As glioma cells express functional CB2 receptors, we used a selective CB2 ligand to target the VEGF pathway. Selective CB2 receptor activation in mice also inhibits the growth and angiogenesis of skin carcinomas.”

“Cannabinoids inhibit tumor angiogenesis…”

“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.full