Category Archives: Breast Cancer

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

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“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

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“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

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“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

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“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

Cannabidiolic acid, a major cannabinoid in fiber-type cannabis, is an inhibitor of MDA-MB-231 breast cancer cell migration.

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“Cannabidiol (CBD), a major non-psychotropic constituent of fiber-type cannabis plant, has been reported to possess diverse biological activities, including anti-proliferative effect on cancer cells. Although CBD is obtained from non-enzymatic decarboxylation of its parent molecule, cannabidiolic acid (CBDA), few studies have investigated whether CBDA itself is biologically active.

Results of the current investigation revealed that CBDA inhibits migration of the highly invasive MDA-MB-231 human breast cancer cells, apparently through a mechanism involving inhibition of cAMP-dependent protein kinase A, coupled with an activation of the small GTPase, RhoA. It is established that activation of the RhoA signaling pathway leads to inhibition of the mobility of various cancer cells, including MDA-MB-231 cells.

The data presented in this report suggest for the first time that as an active component in the cannabis plant, CBDA offers potential therapeutic modality in the abrogation of cancer cell migration, including aggressive breast cancers.”

http://www.ncbi.nlm.nih.gov/pubmed/22963825

“The data presented in this report support the view that CBDA is a biologically active component of the fiber-type cannabis plant with potential utility as an effective anti-migration agent.” http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4009504/

THC inhibits breast cancer cell proliferation through JunD

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“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

THC From Cannabis Destroys Cancer Cells

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“The study results strongly suggest that if taken regularly, cannabis oil may be able to induce remission in leukemia patients without the horrendous side effects typically associated with standard radio-chemical treatment options. Although this is only one such study, other similar studies have shown equally impressive results.

 Many of the active ingredients found in cannabis-derived drugs show exceptional promise in treating some of the greatest hurdles facing modern medical science. In addition to their aforementioned capacity for safely treating certain forms of deadly cancer, they also show great promise in alleviating autoimmune conditions such as rheumatoid arthritis, multiple sclerosis, and even inflammatory bowel disease. A growing number of experts also note their possible viability treating a range of neurological disorders including Alzheimer’s and Lou Gehrig’s disease.”

http://www.globalhealingcenter.com/natural-health/thc-from-cannabis-destroys-cancer-cells/

The Data is Very Strong: Marijuana Plant Extract Stops Cancers From Spreading

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” A compound found in cannabis could halt the spread of many forms of aggressive cancer, scientists say.

Researchers have now found that the compound, called cannabidiol, had the ability to ‘switch off’ the gene responsible for metastasis in an aggressive form of breast cancer. Importantly, this substance does not produce the psychoactive properties of the cannabis plant.

Nonpsychoactive cannabinoids, such as cannabidoil, are particularly advantageous to use because they avoid toxicity that is encountered with psychoactive cannabinoids at high doses useful in the method of the present invention. CBD (Cannabidiol), one of the main constituents of the cannabis plant has been proven medically to relieve many diseases including the inhibition of cancer cell growth. Recent studies have shown it to be an effective atypical anti-psychotic in treating schizophrenia. CBD also interferes with the amount of THC your brain processes, balancing the psychotropic effect of marijuana. That is precisely why the power of raw cannabis is turning heads.”

http://myscienceacademy.org/2012/09/28/the-data-is-very-strong-marijuana-plant-extract-stops-cancers-from-spreading/

Marijuana Compound Fights Cancer; Human Trials Next

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“The “medical” bit of medical marijuana may be legitimate after all: Turns out a component of cannabis fights cancer, according to research.

Scientists at California Pacific Medical Center found that cannabidiol, or CBD, has the ability to “turn off” the DNA that causes “breast and other types of cancers” to metastasize, according to the San Francisco Chronicle.

“If this plant were discovered in the Amazon today, scientists would be falling all over each other to be the first to bring it to market,” said Dr. Donald Abrams, chief of oncology at the University of California San Francisco, which has also found science behind marijuana’s efficacy.”

http://www.nbcbayarea.com/news/local/Marijuana-Compound-Fights-Cancer-Human-Trials-Next-170406116.html

Can Cannabidiol (CBD) Fight Metastatic Cancer? According to the latest research the answer is yes.

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“The article states that scientists at California Pacific Medical Center who have been researching marijuana’s compounds for the 20 years have found that Cannabidiol, or CBD, has the ability to “turn off” the DNA that causes “breast and other types of cancers” to metastasize. CBD is the second-most abundant cannabinoid within marijuana, but does not cause the psychotropic high of THC.

As stated in the article: “We started by researching breast cancer,” said scientist Pierre Desprez. “But now we’ve found that Cannabidiol works with many kinds of aggressive cancers–brain, prostate–any kind in which these high levels of ID-1 are present.””

http://www.walb.com/story/19604192/can-cannabidiol-cbd-fight-metastatic-cancer-according-to-the-latest-research-the-answer-is-yes?fb_action_ids=446062188763761&fb_action_types=og.recommends&fb_source=aggregation&fb_aggregation_id=246965925417366