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Cannabis And Breast Cancer
Posted 11 October 2011 - 09:44 AM
Antitumor Activity of Plant Cannabinoids with Emphasis on the Effect of Cannabidiol on Human Breast Carcinoma
Δ9-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.
THC kills several types of cancer cells, but we refuse to use it simply because it gets you high. So we looked at the other plant cannabinoids that can’t get you high, and wanted to know which would work better, a pure cannabinoid, or Cannabis extracts jazzed up with either more THC, or cannabidiol (CBD).
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 (IC50 between 6.0 and 10.6 μM), 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.
Of the 5 cannabinoids we tested, CBD did the best job slowing the growth of breast cancer cells, while being less toxic to normal cells. The CBD-rich plant extract worked as well as pure CBD, and cannabigerol and cannabichromene were next best.
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.
Both the pure CBD and the CBD-rich plant extract slowed the growth of human breast cancer cells, and thyroid and lung cancer cells that we injected into mice. Judging from several experiments, we think that CBD may kill cancer cells in more than one way.
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 CB2 and vanilloid transient receptor potential vanilloid type-1 receptors and cannabinoid/vanilloid receptor-independent elevation of intracellular Ca2+ and reactive oxygen species. Our data support the further testing of cannabidiol and cannabidiol-rich extracts for the potential treatment of cancer.
In the breast cancer cells we looked at, CBD somehow activates the CB2 and vanilloid receptors and the cancer cell is “told” that it is time to die- and it does! We think that CBD and CBD-rich cannabis extracts are a potential treatment for cancer and we really hope someone else will do another study on this!
Δ9-Tetrahydrocannabinol Inhibits Cell Cycle Progression in Human Breast Cancer Cells through Cdc2 Regulation
It has been proposed that cannabinoids are involved in the control of cell fate. Thus, these compounds can modulate proliferation, differentiation, and survival in different manners depending on the cell type and its physiopathologic context.
It is thought that cannabinoids are involved in what happens to cells. We know they control cell division, what type of cell that a cell eventually becomes, even whether it lives or dies, and it does all these things is several different ways depending on what type of cell it is and where it is.
However, little is known about the effect of cannabinoids on the cell cycle, the main process controlling cell fate. Here, we show that Δ9-tetrahydrocannabinol (THC), through activation of CB2 cannabinoid receptors, reduces human breast cancer cell proliferation by blocking the progression of the cell cycle and by inducing apoptosis. In particular, THC arrests cells in G2-M via down-regulation of Cdc2, as suggested by the decreased sensitivity to THC acquired by Cdc2-overexpressing cells. Of interest, the proliferation pattern of normal human mammary epithelial cells was much less affected by THC.
However, we really don’t know much about what exactly cannabinoids do when it comes to the life and death of a cell. Here we show that THC, by activating the CB 2 receptors, reduces breast cancer growth by blocking the progress of the cancer cell’s reproduction, and telling it to die! In particular THC just slows the cancer cell down. Of interest is that normal cells were much less affected by THC and they reproduced at an almost normal rate.
Cannabidiol induces programmed cell death in breast cancer cells by coordinating the cross-talk between apoptosis and autophagy.
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.
CBD, which comes from the cannabis plant but can’t get you high, is also an anti-cancer drug based on how it kills cancer cells in test tubes and in living organisms. But we don’t know exactly how it kills cancer cells.
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.
Here we show that CBD kills breast cancer cells, in a way we didn’t expect! Somehow CBD sets off two different “die” signals to cancer cells. Our tests confirm this………. (I have edited out the “Sci-Speak” details on just how CBD works to kill the breast cancer cells- I think it’s enough to know that it does kill them!)
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.
Our study shows that CBD causes an interplay between two ways of killing a cancer cell, apoptosis (programed cell death) and autophagy (the cell just self-destructs) and we think it could be used as an anti-cancer medicine!
Cannabis compound stops spread of breast cancer: researchers (2007)
A compound of the marijuana plant may prevent aggressive breast cancers from spreading throughout the body, new research from the United States suggests.
A team of researchers at the California Pacific Medical Center Research Institute say cannabis compound CBD could provide a non-toxic alternative to chemotherapy for cancer treatments. Previous research has shown the compound can block human brain cancers, and recent lab experiments have shown it may be able to do the same for breast cancer.
"Right now we have a limited range of options in treating aggressive forms of cancer. Those treatments, such as chemotherapy, can be effective but they can also be extremely toxic and difficult for patients," said researcher Dr. Sean McAllister in a release. "This compound offers the hope of a non-toxic therapy that could achieve the same results without any of the painful side effects."
CBD works by blocking the activity of gene Id-1, which is associated with metastasis — the spread of cancer cells away from the original tumor site. The compound does not share marijuana's psychoactive properties.
"We know that Id-1 is a key regulator of the spread of breast cancer," said senior author Dr. Pierre-Yves Desprez in a release. "We also know that Id-1 has also been found at higher levels in other forms of cancer. So what is exciting about this study is that if CBD can inhibit Id-1 in breast cancer cells, then it may also prove effective at stopping the spread of cancer cells in other forms of the disease, such as colon and brain or prostate cancer."
Inhibition of Breast Cancer Aggressiveness by Cannabidiol (2006) http://cbcrp.org.127...p?grant_id=4903
An anti-cancer agent with a low toxicity profile that can both inhibit cancer cell growth and metastasis would be extremely valuable clinically. We have discovered that cannabidiol (CBD), a non-psychotropic cannabinoid constituent of the plant Cannabis sativa, can inhibit the growth, migration and invasion of aggressive breast cancer cells in culture. Cannabinoid compounds, in general, have low toxicity profiles.
Furthermore, our preliminary research demonstrated that CBD is a novel inhibitor of a protein whose activity has been closely linked to the aggressiveness of human breast cancers; called inhibitor of DNA binding-1 (Id-1). Whether CBD can inhibit the spread of metastatic breast cancer in vivo (in the body), compared to cell culture conditions, has not been determined.
However, CBD has been demonstrated to inhibit aggressive human brain cancers in vivo. Understanding the mechanisms behind the anti-cancer activity of CBD may lead to the validation of new biological targets for diagnostics and therapies for breast cancer.
To study the effects of CBD on the growth and spread of aggressive breast cancer, we will use time lapse microscopy to capture detailed changes in cell growth/death, migration, and morphology. Classical biochemical measures of cell growth/death and invasion will also be used in combination with novel compounds to identify receptors that CBD interacts with to produce its anti- breast cancer effects.
A mouse model of breast cancer metastasis will be used to determine whether CBD effectively reduces the spread of aggressive breast cancer in vivo. At the intracellular level, we will study whether CBD, (1) regulates Id-1 in an extracellular signal-regulated kinase-dependent manner, and (2) serves to activate a pro-apoptotic (cell death) pathway in a caspase-dependent manner.
Novel and effective non-toxic therapies for aggressive breast cancers are urgently required. Plant cannabinoids are compounds that are well tolerated during chronic (long-term) administration. CBD, and compounds based on its structure, may be the basis for the treatment of metastatic breast cancer.
And remember, to make working CB receptors, you need Omega 3! Cannabis and Omega 3 work hand in hand to heal many diseases! If you have mostly broken CB receptors, cannabis can't heal you!
There are all sorts of news articles about breast cancer right now! Use this opportunity to spread the word that CBD and THC are anti-cancer medicines- and you have the studies to prove it! Become an activist!
All you gotta do is tell the truth! Once the medical facts about cannabis are known, the need for legalization become obvious!
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Posted 11 October 2011 - 09:55 AM
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Posted 11 October 2011 - 10:21 AM
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Posted 12 October 2011 - 10:57 PM
Pathways mediating the effects of cannabidiol on the reduction of breast cancer cell proliferation, invasion, and metastasis. (abst – 2011) Pathways mediating the effects of ca... [Breast Cancer Res Treat. 2011] - PubMed - NCBI
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.
Breast cancer invading and spreading to other parts of the body are the final and fatal steps in this cancer. We don't have many ways to treat aggressive, fast-spreading breast cancers.
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.
We need effective non-toxic medicines NOW! Id-1 stops certain chemicals from being made and this controls how nasty the breast cancer will be. CBD is very safe and slows down Id- 1 in aggressive breast cancers in test tubes.
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.
We tested this in several ways to figure out just how CBD regulated Id- 1, leading to slower growth and spread of aggressive breast cancers.
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.
Then we tried it with mouse breast cancer cells, and we decided on more tests to use to see if CBD would slow breast cancer in living organisms. We show that it does this by using 2 different methods- the ERK, and the ROS, pathways.
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.
CBD also controls ID- 2. In normal mice, CBD not only reduced the main tumors, but also the number and size of new tumors in the lungs!
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.
We think that CBD can be useful in early breast cancers. Our results suggest that CBD could be a new and non-poisonous way to treat breast cancers and we think what we found out about Id-1 and how cannabinoids work in our bodies is very important.
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Posted 16 October 2011 - 04:58 AM
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