Category Archives: Cancer

A new strategy to block tumor growth by inhibiting endocannabinoid inactivation.

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“Endocannabinoid signaling has been shown to be enhanced in several cancer tissues and malignant cells, and studies in cell lines have shown that this up-regulation might serve the purpose of providing transformed cells with a further means to inhibit their proliferation. Here we investigated the effect of inhibitors of endocannabinoid degradation on the growth of rat thyroid tumor xenografts induced in athymic mice. VDM-11, a selective inhibitor of endocannabinoid cellular re-uptake, and arachidonoyl-serotonin (AA-5-HT), a selective blocker of endocannabinoid enzymatic hydrolysis, both inhibited the growth in vivo of tumor xenografts induced by the subcutaneous injection of rat thyroid transformed (KiMol) cells. This effect was accompanied by significantly enhanced endocannabinoid concentrations in the tumors excised at the end of the in vivo experiments. Endocannabinoids, as well as VDM-11 and AA-5-HT, inhibited the growth in vitro of the transformed rat thyroid cells used to induce the tumors in vivo, and their effect was reversed at least in part by the cannabinoid CB1 receptor antagonist SR141716A. This compound, however, when administered alone, did not enhance, but instead slightly inhibited, the growth of rat thyroid transformed cells both in vitro and in tumor xenografts induced in vivo. These findings indicate that endocannabinoids tonically control tumor growth in vivo by both CB1-mediated and non-CB1-mediated mechanisms and that, irrespective of the molecular mechanism of their anti-proliferative action, inhibitors of their inactivation might be used for the development of novel anti-cancer drugs.”  http://www.ncbi.nlm.nih.gov/pubmed/15289448

“A new strategy to block tumor growth by inhibiting endocannabinoid inactivation”  http://www.fasebj.org/content/early/2004/10/02/fj.04-1754fje.long

Cannabinoid 2 receptor induction by IL-12 and its potential as a therapeutic target for the treatment of anaplastic thyroid carcinoma.

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“Anaplastic thyroid carcinoma is the most aggressive type of thyroid malignancies…”

 “These data suggest that CB2 overexpression may contribute to the regression of human anaplastic thyroid tumor… Given that cannabinoids have shown antitumor effects in many types of cancer models, CB2 may be a viable therapeutic target for the treatment of anaplastic thyroid carcinoma.”

http://www.ncbi.nlm.nih.gov/pubmed/18197164

A metabolically stable analogue of anandamide, Met-F-AEA, inhibits human thyroid carcinoma cell lines by activation of apoptosis.

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Abstract

  “The active components of Cannabis sativa and their derivatives produce a wide spectrum of effects, some of which may have clinical application. The discovery of specific cannabinoid receptors and a family of endogenous ligands of those receptors has attracted much attention to cannabinoids as agents capable of controlling the decision of cells to survive or die. We analysed the effects exerted by 2-methyl-2′-F-anandamide (Met-F-AEA), a metabolically stable analogue of anandamide, and observed a growth inhibition in cell lines derived from thyroid carcinomas. Growth inhibition was associated with a high level of CB1 receptor expression, suggesting that the cytotoxic effect is due to interaction with the CB1 receptor. This phenomenon was associated with activation of the protein, p53, an increased apoptotic rate, and expression of p21(CIP1/WAF1). This study provides new insights into the mechanism of Met-F-AEA action, and could have significance in providing a basis for the management of thyroid carcinoma.”

http://www.ncbi.nlm.nih.gov/pubmed/19189054

Naturally occurring and related synthetic cannabinoids and their potential therapeutic applications.

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Abstract

“Naturally occurring cannabinoids (phytocannabinoids) are biosynthetically related terpenophenolic compounds uniquely produced by the highly variable plant, Cannabis sativa L. Natural and synthetic cannabinoids have been extensively studied since the discovery that the psychotropic effects of cannabis are mainly due to Delta(9)-THC. However, cannabinoids exert pharmacological actions on other biological systems such as the cardiovascular, immune and endocrine systems. Most of these effects have been attributed to the ability of these compounds to interact with the cannabinoid CB1 and CB2 receptors. The FDA approval of Marinol, a product containing synthetic Delta(9)-THC (dronabinol), in 1985 for the control of nausea and vomiting in cancer patients receiving chemotherapy, and in 1992 as an appetite stimulant for AIDS patients, has further intensified the research interest in these compounds. This article reviews patents (2003-2007) that describe methods for isolation of cannabinoids from cannabis, chemical and chromatographic methods for their purification, synthesis, and potential therapeutic applications of these compounds.”

http://www.ncbi.nlm.nih.gov/pubmed/19519560

Marijuana May Fight Lung Tumors – FoxNews

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   “…the active ingredient in marijuana may help combat lung cancer, new research suggests.

In lab and mouse studies, the compound, known as THC, cut lung tumor growth in half and helped prevent the cancer from spreading, says Anju Preet, PhD, a Harvard University researcher in Boston who tested the chemical. 

While a lot more work needs to be done, “the results suggest THC has therapeutic potential,” she tells WebMD. 

Moreover, other early research suggests the cannabis compound could help fight brain, prostate, and skin cancers as well, Preet says.”

Read more: http://www.foxnews.com/story/0,2933,266715,00.html

Read more: http://www.foxnews.com/story/0,2933,266715,00.html#ixzz2C1POR7Ap

Antineoplastic activity of cannabinoids.

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   “Lewis lung adenocarcinoma growth was retarded by the oral administration of delta9-tetrahydrocannabinol (delta9-THC), delta8-tetrahydrocannabinol (delta8-THC), and cannabinol (CBN), but not cannabidiol (CBD)… CBD was active only in high concentrations.”

http://www.ncbi.nlm.nih.gov/pubmed/1159836

In vivo effects of cannabinoids on macromolecular biosynthesis in Lewis lung carcinomas.

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Abstract

“Cannabinoids represent a novel class of drugs active in increasing the life span mice carrying Lewis lung tumors and decreasing primary tumor size. In the present studies, the effects of delta9-THC, delta8-THC, and cannabidiol on tumor macromolecular biosynthesis were studied. These drugs inhibit thymidine-3H incorporation into DNA acutely, but did not inhibit leucine uptake into tumor protein. At 24 h after treatment, cannabinoids did not inhibit thymidine-3H incorporation into DNA, leucine-3H uptake into protein or cytidine-3H into RNA.”

http://www.ncbi.nlm.nih.gov/pubmed/616322

Decrease of plasminogen activator inhibitor-1 may contribute to the anti-invasive action of cannabidiol on human lung cancer cells

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“PURPOSE:

Using human lung cancer cells, we evaluated the involvement of plasminogen activator inhibitor-1 (PAI-1) in the anti-invasive action of cannabidiol, a non-psychoactive cannabinoid.”

“RESULTS:

Cannabidiol caused a profound inhibition of A549 cell invasion, accompanied by a decreased expression and secretion of PAI-1… Key data were confirmed in two other human lung cancer cell lines (H460, H358). In vivo, a significant downregulation of PAI-1 protein by cannabidiol was demonstrated in A549 xenografts.”

“CONCLUSION:

Our data provide evidence for a hitherto unknown mechanism underlying the anti-invasive action of cannabidiol on human lung cancer cells.”

http://www.ncbi.nlm.nih.gov/pubmed/20668920

Cannabidiol inhibits cancer cell invasion via upregulation of tissue inhibitor of matrix metalloproteinases-1.

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“Although cannabinoids exhibit a broad variety of anticarcinogenic effects, their potential use in cancer therapy is limited by their psychoactive effects. Here we evaluated the impact of cannabidiol, a plant-derived non-psychoactive cannabinoid, on cancer cell invasion. Using Matrigel invasion assays we found a cannabidiol-driven impaired invasion of human cervical cancer (HeLa, C33A) and human lung cancer cells (A549) that was reversed by antagonists to both CB(1) and CB(2) receptors as well as to transient receptor potential vanilloid 1 (TRPV1). The decrease of invasion by cannabidiol appeared concomitantly with upregulation of tissue inhibitor of matrix metalloproteinases-1 (TIMP-1). Knockdown of cannabidiol-induced TIMP-1 expression by siRNA led to a reversal of the cannabidiol-elicited decrease in tumor cell invasiveness, implying a causal link between the TIMP-1-upregulating and anti-invasive action of cannabidiol. P38 and p42/44 mitogen-activated protein kinases were identified as upstream targets conferring TIMP-1 induction and subsequent decreased invasiveness. Additionally, in vivo studies in thymic-aplastic nude mice revealed a significant inhibition of A549 lung metastasis in cannabidiol-treated animals as compared to vehicle-treated controls.

Altogether, these findings provide a novel mechanism underlying the anti-invasive action of cannabidiol and imply its use as a therapeutic option for the treatment of highly invasive cancers.”  http://www.ncbi.nlm.nih.gov/pubmed/19914218

http://www.sciencedirect.com/science/article/pii/S000629520900971X