Active Component Of Marijuana Has Anti-Cancer Effects, Study Suggests

“Guillermo Velasco and colleagues, at Complutense University, Spain, have provided evidence that suggests that cannabinoids such as the main active component of marijuana (THC) have anticancer effects on human brain cancer cells.

In the study, THC was found to induce the death of various human brain cancer cell lines and primary cultured human brain cancer cells by a process known as autophagy.

Consistent with the in vitro data, administration of THC to mice with human tumors decreased tumor growth and induced the tumor cells to undergo autophagy. As analysis of tumors from two patients with recurrent glioblastoma multiforme (a highly aggressive brain tumor) receiving intracranial THC administration showed signs of autophagy, the authors suggest that cannabinoid administration may provide a new approach to targeting human cancers.”  http://www.sciencedaily.com/releases/2009/04/090401181217.htm

“Cannabinoid action induces autophagy-mediated cell death through stimulation of ER stress in human glioma cells” https://www.jci.org/articles/view/37948

 

Nuvilex Reports Cannabinoid-Based Pancreatic Cancer Treatments to be Developed by Its Subsidiary, Medical Marijuana Sciences, Inc.

“Nuvilex, Inc. (OTCQB:NVLX), international biotechnology and clinical stage provider of natural products and cell and gene therapy solutions for the treatment of diseases, announced today its subsidiary, Medical Marijuana Sciences, Inc., is planning to develop treatments for pancreatic cancer based on cannabinoids from Cannabis sativa.

In 2006, in a publication in the prestigious scientific journal Cancer Research, cannabinoids were reported to cause the death of pancreatic cells in laboratory and animal studies; these results were also seen with human pancreatic cancer cells implanted in mice whose immune systems were suppressed. Since then, laboratory studies have shown that when gemcitabine (Gemzar®), the only drug approved by the FDA as a single agent for the treatment of advanced pancreatic cancer, was combined with three different cannabinoids (each used singly), the growth inhibition was more than additive for six different pancreatic cancer cell lines. When these studies were done with human pancreatic cancer cells in immunosuppressed mice, the antitumor effectiveness of gemcitabine was greatly enhanced. These results, combined with those from other studies not mentioned here, indicate the important potential for developing treatments for pancreatic cancer that include the use of cannabinoids.”

More: http://www.nasdaq.com/article/nuvilex-reports-cannabinoid-based-pancreatic-cancer-treatments-to-be-developed-by-its-subsidiary-medical-marijuana-sciences-inc-20130220-00761

Cannabinoids for Cancer Treatment: Progress and Promise

Cancer Research: 68 (2)

“Cannabinoid refers to a group of chemicals naturally found in the marijuana plant Cannabis sativa L. and includes compounds that are either structurally or pharmacologically similar to Δ(9)-tetrahydrocannabinol or those that bind to the cannabinoid receptors. Although anticancer effects of cannabinoids were shown as early as 1975 in Lewis lung carcinoma, renewed interest was generated little after the discovery of the cannabinoid system and cloning of the specific cannabinoid receptors.

Cannabinoids are a class of pharmacologic compounds that offer potential applications as antitumor drugs, based on the ability of some members of this class to limit inflammation, cell proliferation, and cell survival. In particular, emerging evidence suggests that agonists of cannabinoid receptors expressed by tumor cells may offer a novel strategy to treat cancer. Here, we review recent work that raises interest in the development and exploration of potent, nontoxic, and nonhabit forming cannabinoids for cancer therapy.”

Full Text: http://cancerres.aacrjournals.org/content/68/2/339.long

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

“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

“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

The role of the pancreatic endocannabinoid system in glucose metabolism.

“The endogenous cannabinoid system participates in the regulation of energy homeostasis, and this fact led to the identification of a new group of therapeutic agents for complicated obesity and diabetes. Cannabinoid receptor antagonists are now realities in clinical practice. The use of such antagonists for reducing body weight gain, lowering cholesterol and improving glucose homeostasis is based on the ability of the endocannabinoids to coordinately regulate energy homeostasis by interacting with central and peripheral targets, including adipose tissue, muscle, liver and endocrine pancreas. In this review we will analyse the presence of this system in the main cell types of the islets of Langerhans, as well as the physiological relevance of the endocannabinoids and parent acylethanolamides in hormone secretion and glucose homeostasis. We will also analyse the impact that these findings may have in clinical practice and the potential outcome of new therapeutic strategies for modulating glucose homeostasis and insulin/glucagon secretion.”

http://www.ncbi.nlm.nih.gov/pubmed/19285263

Presence of functional cannabinoid receptors in human endocrine pancreas.

“We examined the presence of functional cannabinoid receptors 1 and 2 (CB1, CB2) in isolated human islets, phenotyped the cells producing cannabinoid receptors and analysed the actions of selective cannabinoid receptor agonists on insulin, glucagon and somatostatin secretion in vitro. We also described the localisation on islet cells of: (1) the endocannabinoid-producing enzymes N-acyl-phosphatidyl ethanolamine-hydrolysing phospholipase D and diacylglycerol lipase; and (2) the endocannabinoid-degrading enzymes fatty acid amidohydrolase and monoacyl glycerol lipase.

RESULTS:

Human islets of Langerhans expressed CB1 and CB2 (also known as CNR1 and CNR2) mRNA and CB1 and CB2 proteins, and also the machinery involved in synthesis and degradation of 2-AG (the most abundant endocannabinoid, levels of which were modulated by glucose). Immunofluorescence revealed that CB1 was densely located in glucagon-secreting alpha cells and less so in insulin-secreting beta cells. CB2 was densely present in somatostatin-secreting delta cells, but absent in alpha and beta cells. In vitro experiments revealed that CB1 stimulation enhanced insulin and glucagon secretion, while CB2 agonism lowered glucose-dependent insulin secretion, showing these cannabinoid receptors to be functional.

CONCLUSIONS/INTERPRETATION:

Together, these results suggest a role for endogenous endocannabinoid signalling in regulation of endocrine secretion in the human pancreas.”

http://www.ncbi.nlm.nih.gov/pubmed/18092149

Gemcitabine/cannabinoid combination triggers autophagy in pancreatic cancer cells through a ROS-mediated mechanism

“Pancreatic adenocarcinoma is one of the most aggressive and devastating human malignancies with a death-to-incidence ratio of 0.99. Although it represents only 2–3% of all cancers, pancreatic adenocarcinoma is the fourth cause of death by tumors…

In recent years, there has been increasing interest in cannabinoids as therapeutic drugs for their antineoplastic, anticachectic, and analgesic potential. Growth inhibitory activities of cannabinoids have been demonstrated for various malignancies, including brain, breast, prostate, colorectal, skin and, recently, pancreatic cancer…

In the present study, we have demonstrated that the combination between the standard chemotherapy agent GEM and cannabinoids synergistically inhibited pancreatic adenocarcinoma cell growth by a ROS-dependent autophagic cell death.

These findings support a key role of the ROS-dependent activation of an autophagic program in the synergistic growth inhibition induced by GEM/cannabinoid combination in human pancreatic cancer cells.

GEM and cannabinoids strongly inhibited growth of human pancreatic adenocarcinoma cells in vivo.”

Read more: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3122066/

US Investigators Praise Cannabinoids As Chemo Treatment

“Cannabinoids inhibit cancer cell proliferation and should be clinically tested as chemotherapeutic agents, according to a review published in the January issue of the journal Cancer Research.

Investigators at the University of Wisconsin School of Medicine and Public Health reported that the administration of cannabinoids halts the spread of a wide range of cancers, including brain cancer, prostate cancer, breast cancer, lung cancer, skin cancer, pancreatic cancer, and lymphoma.

Researchers suggested that cannabinoids may offer significant advantages over standard chemotherapy treatments because the compounds are both non-toxic and can uniquely target malignant cells while ignoring healthy ones.

“Cannabinoids … offer potential applications as anti-tumor drugs, based on the ability of some members of this class to limit inflammation, cell proliferation, and cell survival,” authors concluded. “[T]here is overwhelming evidence to suggest that cannabinoids can be explored as chemotherapeutic agents for the treatment of cancer.””

Read more: http://norml.org/news/2008/01/31/us-investigators-praise-cannabinoids-as-chemo-treatment

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