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. 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.

“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

“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?

“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

Cannabis destroys cancer cells

“Scientists working in the UK have revealed that cannabis has the potential to destroy leukemia cells.

The team – based at Queen Mary’s School of Medicine and Dentistry in London – have followed up on their previous findings that the main active ingredient in cannabis, tetrahydrocannabinol (THC) has the potential to be used effectively against some forms of cancer.

THC has previously been shown to attack cancer cells by interfering with important growth-processing pathways, however its mechanism of doing so has remained a mystery. Now, Dr Liu and his colleagues, using microarray technology – allowing them to simultaneously detect changes in more than 18,000 genes in cells treated with THC – have begun to uncover the existence of processes through which THC can kill cancer cells and potentially promote survival.”

http://www.labnews.co.uk/news/cannabis-destroys-cancer-cells/

 

THC From Cannabis Destroys Cancer Cells

“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

” 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/

Cannabis Oil Fights Cancer

“Oil extracted from the marijuana plant has been shown to have extraordinary cancer-fighting properties.

A number of recent studies have confirmed the cancer-fighting, tumor-shrinking value of medical marijuana.

Although the first study to demonstrate that cannabis has anti-carcinogenic properties was done  back in 1974 by the U.S. National Institute of Health, more recent studies, which began abroad in 1999, have shown that cannabis can effectively and safely treat many forms of cancer.

Since 1999, there have now been a number of studies that clearly demonstrate that cannabis has the ability to effectively shrink tumors, kill cancer cells, and safely treat many aggressive forms of cancer, including brain, breast, skin, prostate, and lung cancer.

However, due to the political controversy that surrounds medical marijuana, some physicians still remain unaware of these valuable studies, and mistakenly believe the misguided government reports that cannabis actually causes cancer. In some cases, it may be important to educate your doctor about the important research discussed in this column.”

http://themidwestcultivator.com/marijuana-news-health/08-2011/cannabis-oil-fights-cancer

Marijuana May Fight Lung Tumors – CBSNews

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

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

The finding builds on the recent discovery of the body’s own cannabinoid system, Preet says. Known as endocannabinoids, the natural cannabinoids stimulate appetite and control pain and inflammation.

THC seeks out, attaches to, and activates two specific endocannabinoids that are present in high amounts on lung cancer cells, Preet says. This revs up their natural anti-inflammatory properties. Inflammation can promote the growth and spread of cancer.

In the new study, the researchers first demonstrated that THC inhibited the growth and spread of cells from two different lung cancer cell lines and from patient lung tumors. Then, they injected THC into mice that had been implanted with human lung cancer cells. After three weeks, tumors shrank by about 50 percent, compared with tumors in untreated mice.”

 http://www.cbsnews.com/2100-500368_162-2696726.html

Marijuana Compound Fights Cancer; Human Trials Next

“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