Cannabinoids fight pancreatic cancer

Cannabinoids which work via the CB1 and CB2 receptor, as does THC from marijuana, interfere with pancreatic cancer's cellular metabolism, causing the cancer cells to die off. The following abstract is quite technical but what you need to consider is the final line which reports that cannabinoids killed off and stunted the growth of pancreatic cancer cells. Cell Death Dis. 2013 Jun 13;4:e664. doi: 10.1038/cddis.2013.151.Cannabinoids inhibit energetic metabolism and induce AMPK-dependent autophagy in pancreatic cancer cells.Dando I, Donadelli M, Costanzo C, Dalla Pozza E, D'Alessandro A, Zolla L, Palmieri M.SourceDepartment of Life and Reproduction Sciences, Biochemistry Section, University of Verona, Verona, Italy. Abstract: The anti-tumoral effects of cannabinoids have been described in different tumor systems, including pancreatic adenocarcinoma, but their mechanism of action remains unclear. We used cannabinoids specific for the CB1 ACPA and CB2 GW receptors and metabolomic analyses to unravel the potential pathways mediating cannabinoid-dependent inhibition of pancreatic cancer cell growth. Panc1 cells treated with cannabinoids show elevated AMPK activation induced by a ROS-dependent increase of AMP/ATP ratio. ROS promote nuclear translocation of GAPDH, which is further amplified by AMPK, thereby attenuating glycolysis. Furthermore, ROS determine the accumulation of NADH, suggestive of a blockage in the respiratory chain, which in turn inhibits the Krebs cycle. Concomitantly, inhibition of Akt/c-Myc pathway leads to decreased activity of both the pyruvate kinase isoform M2 PKM2, further downregulating glycolysis, and glutamine uptake. Altogether, these alterations of pancreatic cancer cell metabolism mediated by cannabinoids result in a strong induction of autophagy and in the inhibition of cell growth.

via Cannabinoids inhibit energetic metabolism and... [Cell Death Dis. 2013] - PubMed - NCBI.

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

The non-psychoactive cannabinoid CBD has powerful anti-tumor effects without toxic side-effects! It is only available at medical marijuana dispensaries, in certain states with protections for cannabis-using patients. Hopefully the war on dispensaries will end in Obama's 2nd term because street dealers do not sell cannabis products that don't get you high. If someone you love has breast cancer or another serious cancer, get to a medical state and get some CBD marijuana, or better yet concentrate. And raise hell to your elected officials about how prohibition harms us all! It's time to humiliate the defenders of this immoral prohibition policy as enemies of public health and human decency. Cannabidiol as a novel inhibitor of Id-1 gene expression in aggressive breast cancer cells

Sean D. McAllister, et al.

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. [Mol Cancer Ther 2007;611:2921–7]

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

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

The non-psychoactive cannabinoid CBD has powerful anti-tumor effects without toxic side-effects! It is only available at medical marijuana dispensaries, in certain states with protections for cannabis-using patients. Hopefully the war on dispensaries will end in Obama's 2nd term because street dealers do not sell cannabis products that don't get you high. If someone you love has breast cancer or another serious cancer, get to a medical state and get some CBD marijuana, or better yet concentrate. And raise hell to your elected officials about how prohibition harms us all! It's time to humiliate the defenders of this immoral prohibition policy as enemies of public health and human decency. Cannabidiol as a novel inhibitor of Id-1 gene expression in aggressive breast cancer cells

Sean D. McAllister, et al.

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. [Mol Cancer Ther 2007;611:2921–7]

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

Unbound MEDLINE | Tumor necrosis factor activation of vagal afferent terminal calcium is blocked by cannabinoids. PubMed Journal article abstract

This explains one way in which cannabis is effective against such a wide variety of illnesses, it reduces the level of tumor necrosis factor in the body. Rogers RC, Hermann GE

Tumor necrosis factor activation of vagal afferent terminal calcium is blocked by cannabinoids. [Journal Article, Research Support, N.I.H., Extramural]

J Neurosci 2012 Apr 11; 32(15):5237-41.

The early proinflammatory cytokine tumor necrosis factor (TNF) is released in significant quantities by the activated immune system in response to infection, leukemia, autoimmune disorders, and radiation sickness. Nausea, emesis, and anorexia are common features of these disorders. TNF action on vagal afferent terminals in the brainstem is a likely cause of the malaise associated with these disorders. Our previous work has shown that TNF action to excite vagal afferents occurs as a result of sensitization of ryanodine channels in afferent nerve terminals. For millennia, cannabinoids (CB) have been used to combat the visceral malaise associated with chronic disease, although the mechanism of action has not been clear. Previous work in culture systems suggests that CB1 agonists can suppress neurotransmission by downregulating ryanodine channels through a protein kinase A (PKA)-dependent mechanism. Laser confocal calcium imaging methods were used to directly examine effects of CB1 cannabinoid agonists and TNF on visceral afferent signaling in the rat hindbrain. CB1 agonists blocked the effects of TNF to amplify vagal afferent responsiveness; blockade of PKA with H89 also eliminated the TNF amplification effect. These results help to explain the effectiveness of cannabinoids in blocking the malaise generated by TNF-releasing disease processes by opposing effects on ryanodine channels.

via Unbound MEDLINE | Tumor necrosis factor activation of vagal afferent terminal calcium is blocked by cannabinoids. PubMed Journal article abstract.