Tag Archives: CBD

Pot compound seen as tool against cancer

Posted on by
Reply

“Marijuana, already shown to reduce pain and nausea in cancer patients, may be promising as a cancer-fighting agent against some of the most aggressive forms of the disease.

A growing body of early research shows a compound found in marijuana – one that does not produce the plant’s psychotropic high – seems to have the ability to “turn off” the activity of a gene responsible for metastasis in breast and other types of cancers.

Two scientists at San Francisco’s California Pacific Medical Center Research Institute first released data five years ago that showed how this compound – called cannabidiol – reduced the aggressiveness of human breast cancer cells in the lab.”

Marijuana’s better known cannabinoid – delta-9 tetrahydrocannabinol, or THC – had already shown some anticancer properties in tumors, but the non-psychotropic cannabidiol had largely gone unstudied. McAllister initial research showed CBD had anticancer potential as well.”

http://www.sfgate.com/health/article/Pot-compound-seen-as-tool-against-cancer-3875562.php

Marijuana compound could stop aggressive cancer metastasis

Posted on by
Reply

“A compound found in cannabis could halt the spread of many forms of aggressive cancer, scientists have claimed.

Researchers found that the compound, called cannabidiol, had the ability to “switch off” the gene responsible for metastasis in an aggressive form of breast cancer, the Daily Mail reported.

Importantly, this substance does not produce the psychoactive properties of the cannabis plant.

The team from the California Pacific Medical Center, in San Francisco, first spotted its potential five years ago, after it stopped the proliferation of human breast cancer cells in the lab, the report said.

They discovered that the compound had turned off the overexpression of ID-1, stopping them from travelling to distant tissues.

Other potentially treatable cancers are forms of leukaemia, lung, ovarian and brain cancers, which also have high levels of ID-1.”

http://in.news.yahoo.com/marijuana-compound-could-stop-aggressive-cancer-metastasis-064950912.html

Endocannabinoids in endocrine and related tumours.

Posted on by
Reply

“The ‘endocannabinoid system’, comprising the cannabinoid CB1 and CB2 receptors, their endogenous ligands, endocannabinoids and the enzymes that regulate their biosynthesis and degradation, has drawn a great deal of scientist attention during the last two decades. The endocannabinoid system is involved in a broad range of functions and in a growing number of physiopathological conditions. Indeed, recent evidence indicates that endocannabinoids influence the intracellular events controlling the proliferation of numerous types of endocrine and related cancer cells, thereby leading to both in vitro and in vivo antitumour effects. In particular, they are able to inhibit cell growth, invasion and metastasis of thyroid, breast and prostate tumours. The chief events of endocannabinoids in cancer cell proliferation are reported highlighting the correspondent signalling involved in tumour processes: regulation of adenylyl cyclase, cyclic AMP-protein kinase-A pathway and MEK-extracellular signal-regulated kinase signalling cascade.

Up to date since the isolation and characterisation of the psychoactive component of Cannabis sativa, Δ9-tetrahydrocannabinol (Δ9-THC), about 60 different plant terpeno-phenols more or less related to THC have been isolated and defined cannabinoids. They include cannabidiol (CBD), cannabinol, cannabigerol and cannabichromene. The discovery of these principles stimulated the generation of a whole range of synthetic analogues that included not only compounds structurally similar to phytocannabinoids, but also analogues with different chemical structures, including classic and non-classic cannabinoids and aminoalkylindoles (Howlett et al. 2002) as well as the subsequently discovered endogenous arachidonic acid derivatives or endocannabinoids. The discovery of this family of endogenous cannabinoids (Devane et al. 1992, Mechoulam et al. 1995, Sugiura et al. 1995) has focused much attention on cannabinoids and their pharmacological properties during the last few years (Di Marzo et al. 2004).”

http://erc.endocrinology-journals.org/content/15/2/391.long

CANNABIDIOL AS POTENTIAL ANTICANCER DRUG.

Posted on by
Reply

“Over the past years, several lines of evidence support an antitumorigenic effect of cannabinoids including Δ(9) -tetrahydrocannabinol (Δ(9) -THC), synthetic agonists, endocannabinoids and endocannabinoid transport or degradation inhibitors. Indeed, cannabinoids possess anti-proliferative and pro-apoptotic effects and they are known to interfere with tumour neovascularization, cancer cell migration, adhesion, invasion and metastasization. However, the clinical use of Δ(9) -THC and additional cannabinoid agonists is often limited by their unwanted psychoactive side effects, and for this reason interest in non-psychoactive cannabinoid compounds with structural affinity for Δ(9) -THC, such as cannabidiol (CBD), has substantially increased in recent years. The present review will focus on the efficacy of CBD in the modulation of different steps of tumourigenesis in several types of cancer and highlights the importance of exploring CBD/CBD analogues as alternative therapeutic agents.”

http://www.ncbi.nlm.nih.gov/pubmed/22506672

Antitumor Activity of Plant Cannabinoids with Emphasis on the Effect of Cannabidiol on Human Breast Carcinoma

Posted on by
Reply

“Delta(9)-Tetrahydrocannabinol (THC) exhibits antitumor effects on various cancer cell types, but its use in chemotherapy is limited by its psychotropic activity. We investigated the antitumor activities of other plant cannabinoids, i.e., cannabidiol, cannabigerol, cannabichromene, cannabidiol acid and THC acid, and assessed whether there is any advantage in using Cannabis extracts (enriched in either cannabidiol or THC) over pure cannabinoids. Results obtained in a panel of tumor cell lines clearly indicate that, of the five natural compounds tested, cannabidiol is the most potent inhibitor of cancer cell growth (IC(50) between 6.0 and 10.6 microM), with significantly lower potency in noncancer cells. The cannabidiol-rich extract was equipotent to cannabidiol, whereas cannabigerol and cannabichromene followed in the rank of potency. Both cannabidiol and the cannabidiol-rich extract inhibited the growth of xenograft tumors obtained by s.c. injection into athymic mice of human MDA-MB-231 breast carcinoma or rat v-K-ras-transformed thyroid epithelial cells and reduced lung metastases deriving from intrapaw injection of MDA-MB-231 cells. Judging from several experiments on its possible cellular and molecular mechanisms of action, we propose that cannabidiol lacks a unique mode of action in the cell lines investigated. At least for MDA-MB-231 cells, however, our experiments indicate that cannabidiol effect is due to its capability of inducing apoptosis via: direct or indirect activation of cannabinoid CB(2) and vanilloid transient receptor potential vanilloid type-1 receptors and cannabinoid/vanilloid receptor-independent elevation of intracellular Ca(2+) and reactive oxygen species. Our data support the further testing of cannabidiol and cannabidiol-rich extracts for the potential treatment of cancer.”

In conclusion, our data indicate that cannabidiol, and possibly Cannabis extracts enriched in this natural cannabinoid, represent a promising nonpsychoactive antineoplastic strategy. In particular, for a highly malignant human breast carcinoma cell line, we have shown here that cannabidiol and a cannabidiol-rich extract counteract cell growth both in vivo and in vitro as well as tumor metastasis in vivo. Cannabidiol exerts its effects on these cells through a combination of mechanisms that include either direct or indirect activation of CB2 and TRPV1 receptors and induction of oxidative stress, all contributing to induce apoptosis. Additional investigations are required to understand the mechanism of the growth-inhibitory action of cannabidiol in the other cancer cell lines studied here.”

http://jpet.aspetjournals.org/content/318/3/1375.long

Cannabidiol as a novel inhibitor of Id-1 gene expression in aggressive breast cancer cells

Posted on by
Reply

“Invasion and metastasis of aggressive breast cancer cells is the final and fatal step during cancer progression, and is the least understood genetically. Clinically, there are still limited therapeutic interventions for aggressive and metastatic breast cancers available. Clearly, effective and nontoxic therapies are urgently required. Id-1, an inhibitor of basic helix-loop-helix transcription factors, has recently been shown to be a key regulator of the metastatic potential of breast and additional cancers. Using a mouse model, we previously determined that metastatic breast cancer cells became significantly less invasive in vitro and less metastatic in vivo when Id-1 was down-regulated by stable transduction with antisense Id-1. It is not possible at this point, however, to use antisense technology to reduce Id-1 expression in patients with metastatic breast cancer. Here, we report that cannabidiol (CBD), a cannabinoid with a low-toxicity profile, could down-regulate Id-1 expression in aggressive human breast cancer cells. The CBD concentrations effective at inhibiting Id-1 expression correlated with those used to inhibit the proliferative and invasive phenotype of breast cancer cells. CBD was able to inhibit Id-1 expression at the mRNA and protein level in a concentration-dependent fashion. These effects seemed to occur as the result of an inhibition of the Id-1 gene at the promoter level. Importantly, CBD did not inhibit invasiveness in cells that ectopically expressed Id-1. In conclusion, CBD represents the first nontoxic exogenous agent that can significantly decrease Id-1 expression in metastatic breast cancer cells leading to the down-regulation of tumor aggressiveness.

Cannabinoids Reduce the Growth of Aggressive Human Breast Cancer Cells”

Cannabinoids Reduce Breast Cancer Cell Invasiveness

CBD Down-regulates Id-1 Expression

The Effects of CBD on Invasion and Id-1 Protein Expression Can Be Reproduced in an Additional Breast Cancer Cell Line

Plant cannabinoids are stable compounds with low-toxicity profiles that are well tolerated by animals and humans during chronic administration. 

If CBD shows efficacy for treatment of metastatic breast cancer in humans, the low toxicity of the compound would make it an ideal candidate for chronic administration.”

http://mct.aacrjournals.org/content/6/11/2921.long

Pathways mediating the effects of cannabidiol on the reduction of breast cancer cell proliferation, invasion, and metastasis

Posted on by
1

“Invasion and metastasis of aggressive breast cancer cells are the final and fatal steps during cancer progression. Clinically, there are still limited therapeutic interventions for aggressive and metastatic breast cancers available. Therefore, effective, targeted, and non-toxic therapies are urgently required. Id-1, an inhibitor of basic helix-loop-helix transcription factors, has recently been shown to be a key regulator of the metastatic potential of breast and additional cancers. We previously reported that cannabidiol (CBD), a cannabinoid with a low toxicity profile, down-regulated Id-1 gene expression in aggressive human breast cancer cells in culture. Using cell proliferation and invasion assays, cell flow cytometry to examine cell cycle and the formation of reactive oxygen species, and Western analysis, we determined pathways leading to the down-regulation of Id-1 expression by CBD and consequently to the inhibition of the proliferative and invasive phenotype of human breast cancer cells. Then, using the mouse 4T1 mammary tumor cell line and the ranksum test, two different syngeneic models of tumor metastasis to the lungs were chosen to determine whether treatment with CBD would reduce metastasis in vivo. We show that CBD inhibits human breast cancer cell proliferation and invasion through differential modulation of the extracellular signal-regulated kinase (ERK) and reactive oxygen species (ROS) pathways, and that both pathways lead to down-regulation of Id-1 expression. Moreover, we demonstrate that CBD up-regulates the pro-differentiation factor, Id-2. Using immune competent mice, we then show that treatment with CBD significantly reduces primary tumor mass as well as the size and number of lung metastatic foci in two models of metastasis. Our data demonstrate the efficacy of CBD in pre-clinical models of breast cancer. The results have the potential to lead to the development of novel non-toxic compounds for the treatment of breast cancer metastasis, and the information gained from these experiments broaden our knowledge of both Id-1 and cannabinoid biology as it pertains to cancer progression.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3410650/

Cannabidiol Induces Programmed Cell Death in Breast Cancer Cells by Coordinating the Cross-talk between Apoptosis and Autophagy

Posted on by
2

“Cannabidiol (CBD), a major nonpsychoactive constituent of cannabis, is considered an antineoplastic agent on the basis of its in vitro and in vivo activity against tumor cells. However, the exact molecular mechanism through which CBD mediates this activity is yet to be elucidated. Here, we have shown CBD-induced cell death of breast cancer cells, independent of cannabinoid and vallinoid receptor activation. Electron microscopy revealed morphologies consistent with the coexistence of autophagy and apoptosis. Western blot analysis confirmed these findings. We showed that CBD induces endoplasmic reticulum stress and, subsequently, inhibits AKT and mTOR signaling as shown by decreased levels of phosphorylated mTOR and 4EBP1, and cyclin D1. Analyzing further the cross-talk between the autophagic and apoptotic signaling pathways, we found that beclin1 plays a central role in the induction of CBD-mediated apoptosis in MDA-MB-231 breast cancer cells. Although CBD enhances the interaction between beclin1 and Vps34, it inhibits the association between beclin1 and Bcl-2. In addition, we showed that CBD reduces mitochondrial membrane potential, triggers the translocation of BID to the mitochondria, the release of cytochrome c to the cytosol, and, ultimately, the activation of the intrinsic apoptotic pathway in breast cancer cells. CBD increased the generation of reactive oxygen species (ROS), and ROS inhibition blocked the induction of apoptosis and autophagy. Our study revealed an intricate interplay between apoptosis and autophagy in CBD-treated breast cancer cells and highlighted the value of continued investigation into the potential use of CBD as an antineoplastic agent.”

http://mct.aacrjournals.org/content/10/7/1161.long

THC inhibits breast cancer cell proliferation through JunD

Posted on by
3

“Tetrahydrocannabinol is a potent inhibitor of proliferation in cultured breast cancer cells and exerts its effect through the JunD transcription factor complex, researchers report.

There is increasing evidence that cannabinoids, the active components of marijuana, possess antitumoral properties by inhibiting proliferation and angiogenesis or promoting apoptosis.

A previous study reported by MedWire News showed that cannabidiol, a non-toxic phytocannabinoid, can inhibit breast cancer spread in a rodent model of the disease.

In the present study, Cristina Sanchez (Complutense University, Madrid, Spain) and colleagues turned their attention to the more potent plant-derived cannabinoid, Δ9-tetrahydrocannabinol (THC).

“These findings point therefore to a new target to inhibit breast cancer progression, which may contribute to the design of efficient treatments for this malignancy,’ Sanchez et al conclude in the journal Oncogene.”

http://www.medwire-news.md/46/74849/Oncology/THC_inhibits_breast_cancer_cell_proliferation_through_JunD.html

No medical benefit from marijuana? How about a cancer cure?

Posted on by
Reply

“It’s been known for a long time that THC and other cannabinoids can effectively treat symptoms of cancer sufferers and chemotherapy patients, such as nausea, pain, loss of appetite and fatigue. But what scientists have proven in laboratory experiments and testing on animals the last few years is that cannabinoids also can kill cancer cells and stop the spread of aggressive types of the disease — cancer of the breast, brain, prostate, colon or lungs.

The way cannabinoids work, simply put, is by blocking or deactivating a gene called ID-1 that spreads cancer. One compound that’s been found to be especially effective doing this is called cannabidiol, or CBD.

Also, CBD (which unlike THC is non-psychoactive) and other cannabinoids are non-toxic, which greatly reduces the risk of harmful effects from their use.”

http://kpbj.com/opinions/editors_view/2012-10-02/no_medical_benefit_from_marijuana_how_about_a_cancer_cure