Toke and Poke:Cannabis and Breast Cancer

October is Breast Cancer Awareness month and its in full swing.  To help celebrate the lives lost as well as saved, we have gathered research that shows cannabis to be a useful treatment option not only for symptoms but for cancer itself.  With more research we can prove that cannabis does have medicinal value and can greatly aid or cure many ailments.  These are published medical studies that I encourage you to research and share your findings with everyone.  Spread the truth!
Information gathered by David Worrell edited by Cherry Girl
Self examination is still a great way for early detection so don’t for get to toke and poke at least once a month.  (Video at bottom or page)

Cause:

Activation of Multiple Cancer-Associated Genes At the ERBB2 Amplicon in Breast Cancer
The ERBB2 (neu/HER2) oncogene, located at chromosome 17q12, is one of the most intensively studied genes in cancer, especially in breast cancer.
Kauraniemi P, Kallioniemi A. SourceLaboratory of Cancer Biology, University of Tampere and Tampere University Hospital, 33014 Tampere, Finland. paivikki.kauraniemi@uta.fi

Abstract
During the past decade the role of the ERBB2 (neu/HER2) oncogene as an important predictor of patient outcome and response to various therapies in breast cancer has been clearly established. This association of ERBB2 aberrations with more aggressive disease and poor clinical outcome, together with the high prevalence of such alterations in breast cancer, has also made ERBB2 an attractive target for therapy. A specific antibody-based therapy, Herceptin, directed against the extracellular domain of the ERBB2 receptor tyrosine kinase, was recently developed and several clinical trials have shown the therapeutic efficacy of this drug against ERBB2-positive breast cancer. However, a relatively large fraction of patients does not benefit from Herceptin treatment, indicating that other factors beyond ERBB2 itself must influence therapy response in ERBB2-positive tumors. It is well known that amplification of the 17q12-q21 region is the most common mechanism for ERBB2 activation in breast cancer and that it leads to simultaneous activation of several other genes. These co-amplified and co-activated genes may have an impact on disease progression and the clinical behavior of ERBB2-positive tumors and thus represent important targets of research. In this paper we discuss the current knowledge on the structure of the ERBB2 amplicon, the genes involved, and their possible contribution to breast cancer pathogenesis.”
http://erc.endocrinology-journals.org/content/13/1/39.long

CURE:

Cannabinoids Reduce ErbB2-Driven Breast Cancer Progression Through Akt Inhibition
“Taken together, these results provide a strong preclinical evidence for the use of cannabinoid-based therapies for the management of ErbB2-positive breast cancer.”
‎”Cannabinoids reduce ErbB2-driven breast cancer progression through Akt inhibition.  Caffarel MM, Andradas C, Mira E, Pérez-Gómez E, Cerutti C, Moreno-Bueno G, Flores JM, García-Real I, Palacios J, Mañes S, Guzmán M, Sánchez C.
SourceDept, Biochemistry and Molecular Biology I, School of Biology, Complutense University, Madrid, Spain.

Abstract
BACKGROUND: ErbB2-positive breast cancer is characterized by highly aggressive phenotypes and reduced responsiveness to standard therapies. Although specific ErbB2-targeted therapies have been designed, only a small percentage of patients respond to these treatments and most of them eventually relapse. The existence of this population of particularly aggressive and non-responding or relapsing patients urges the search for novel therapies. The purpose of this study was to determine whether cannabinoids might constitute a new therapeutic tool for the treatment of ErbB2-positive breast tumors. We analyzed their antitumor potential in a well established and clinically relevant model of ErbB2-driven metastatic breast cancer: the MMTV-neu mouse. We also analyzed the expression of cannabinoid targets in a series of 87 human breast tumors.

RESULTS: Our results show that both Delta9-tetrahydrocannabinol, the most abundant and potent cannabinoid in marijuana, and JWH-133, a non-psychotropic CB2 receptor-selective agonist, reduce tumor growth, tumor number, and the amount/severity of lung metastases in MMTV-neu mice. Histological analyses of the tumors revealed that cannabinoids inhibit cancer cell proliferation, induce cancer cell apoptosis, and impair tumor angiogenesis. Cannabinoid antitumoral action relies, at least partially, on the inhibition of the pro-tumorigenic Akt pathway. We also found that 91% of ErbB2-positive tumors express the non-psychotropic cannabinoid receptor CB2.

CONCLUSIONS: Taken together, these results provide a strong preclinical evidence for the use of cannabinoid-based therapies for the management of ErbB2-positive breast cancer.”

The Expression Level of CB1 and CB2 Receptors Determines Their Efficacy at Inducing Apoptosis in Ast

‎”The high expression level of CB1 and CB2 receptors commonly found in malignant astrocytomas precludes the use of cannabinoids as therapeutics, unless AKT is concomitantly inhibited, or cannabinoids are applied at concentrations that bypass CB1 and CB2 receptors, yet still activate ERK1/2.” So, for astrocytomas, cannabinoids can only be used if they inhibit AKT and activate ERK1/2.
“The expression level of CB1 and CB2 receptors determines their efficacy at inducing apoptosis in astrocytomas. Cudaback E, Marrs W, Moeller T, Stella N.
SourceDepartment of Pharmacology, University of Washington, Seattle, Washington, United States of America.

Abstract
BACKGROUND: Cannabinoids represent unique compounds for treating tumors, including astrocytomas. Whether CB(1) and CB(2) receptors mediate this therapeutic effect is unclear.

PRINCIPAL FINDINGS: We generated astrocytoma subclones that express set levels of CB(1) and CB(2), and found that cannabinoids induce apoptosis only in cells expressing low levels of receptors that couple to ERK1/2. In contrast, cannabinoids do not induce apoptosis in cells expressing high levels of receptors because these now also couple to the prosurvival signal AKT. Remarkably, cannabinoids applied at high concentration induce apoptosis in all subclones independently of CB(1), CB(2) and AKT, but still through a mechanism involving ERK1/2.

SIGNIFICANCE: The high expression level of CB(1) and CB(2) receptors commonly found in malignant astrocytomas precludes the use of cannabinoids as therapeutics, unless AKT is concomitantly inhibited, or cannabinoids are applied at concentrations that bypass CB(1) and CB(2) receptors, yet still activate ERK1/2.”
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2806825/?tool=pubmed

Cannabidiol Induces Programmed Cell Death In Breast Cancer Cells By Coordinating the Cross-Talk Between Apoptosis and Autophagy
‎”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.”
“Cannabidiol induces programmed cell death in breast cancer cells by coordinating the cross-talk between apoptosis and autophagy.
Shrivastava A, Kuzontkoski PM, Groopman JE, Prasad A. Source Division of Experimental Medicine, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215, USA. abailugu@bidmc.harvard.edu

Abstract
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://www.ncbi.nlm.nih.gov/pubmed/21566064

Medical Marijuana Stops Spread of Breast Cancer – NBC NEWS