“Medical Marijuana” Takes On New Meaning for Metastatic Breast Cancer

[grammychronic]

If you have breast cancer, you may have considered the use of “medical marijuana” at some point during your chemo treatment (http://www.healthcentral.com/breast-cancer/coping-with-chemotherapy.html). Smoking marijuana has provided some women with relief from the nausea and vomiting that can accompany chemo, relief that the range of normal side effect drugs weren’t able to give. Some states permit the legal use of medical marijuana; most don’t. Nevertheless, most women who want to try marijuana seem to be able to get it. Personally, I didn’t experience any severe problems with nausea. But I was astounded at the number of people who, prior to treatment, offered to get me a supply if I thought I needed it!

Now, doctors at the California Pacific Medical Center Research Institute in San Francisco have released a study, in the current issue of Molecular Cancer Therapeutics, that may in the future open the door to a much more critical use of marijuana: stopping the spread of metastatic breast cancer. It seems that a compound found in cannabis (the scientific name for marijuana), CBD, has been shown (in the lab) to stop the human gene Id-1 from directing cancer cells to multiply and spread.

California Pacific Senior researcher Pierre-Yves Desprez, in an interview with HealthDay News, noted that the Id-1 genes “are very bad (http://www.healthcentral.com/breast-cancer/news-195837-31.html). They push the cells to behave like embryonic cells and grow. They go crazy, they proliferate, they migrate. We need to be able to turn them off."

http://www.healthcentral.com/breast-cancer/c/78/16646/takes-cancer/

[Sequoiacrone]

Cannabidiol as a novel inhibitor of Id-1 gene expression
in aggressive breast cancer cells
Sean D. McAllister, Rigel T. Christian,
Maxx P. Horowitz, Amaia Garcia,
and Pierre-Yves Desprez
California Pacific Medical Center, Research Institute,
San Francisco, California
Abstract
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;6(11):2921–7]
Introduction
The development of breast cancer and its spread to other
parts of the body requires several genotypic and phenotypic
changes in the cells leading to de-differentiation,
uncontrolled proliferation, and invasion. Invasion and
metastasis to the other tissues of the body is the final and
fatal step during cancer progression and is the least
understood genetically (1). Despite all currently available
treatments, breast cancer is most often incurable once
clinically apparent metastases develops.
Id helix-loop-helix proteins are negative regulators of
basic helix-loop-helix transcription factors (2). Strong evidence
now suggests that the Id family of helix-loop-helix
proteins control cellular processes related to tumor progression
(3). We found that reducing Id-1 using antisense
technology led to significant reductions in breast cancer
cell proliferation and invasiveness in vitro and metastasis
in vivo in mice (4). Furthermore, Id-1 overexpression in
breast cancer cells was also found to be one of the most
significant genes within a gene signature set that is correlated
with the propensity of primary human breast cancer
cells to metastasize to the lung (5).
Reducing Id-1 expression could provide a rational
therapeutic strategy for the treatment of aggressive human
breast cancers. It is not possible at this point, however,
to use antisense technology to reduce Id-1 expression in
humans with metastatic breast cancer. In our search for a
nontoxic exogenous compound that could inhibit Id-1 expression,
a potential candidate agent, cannabidiol (CBD),
was discovered.
The endocannabinoid system was discovered through
research focusing on the primary psychoactive component
of Cannabis sativa, D9-tetrahydrocannabinol (D9-THC), and
other synthetic cannabinoids (6). D9-THC and additional
cannabinoid agonists have been shown to interact with two
G protein–coupled receptors named CB1 and CB2 (6). More
recent studies have shown that CB1 and CB2 receptor
agonists show promise as tumor inhibitors (7, 8). The
psychotropic effects of D9-THC and additional cannabinoid
agonists, mediated through the CB1 receptor, limit their
clinical utility. In addition to D9-THC, CBD is also present
in significant quantities in C. sativa (9). CBD does not have
appreciable affinity for CB1 or CB2 receptors and does not
have psychotropic activities (10). CBD has been shown to
inhibit breast cancer metastasis in vivo in mice (11).
However, modulation of a distinct signaling pathway that
would explain the inhibitory action of CBD on breast

TO READ THE ENTIRE ARTICLE
http://www.letfreedomgrow.com/cmu/cbd_breast_cancer.pdf


source and reprints

Received 6/4/07; revised 9/5/07; accepted 9/20/07.
Grant support:



NIH (CA102412, CA111723, DA09978, and CA82548),

the Department of Defense (PC041013), the California Breast Cancer
Research Program (12IB-0116), and the Research Institute at California
Pacific Medical Center.
The costs of publication of this article were defrayed in part by the
payment of page charges. This article must therefore be hereby marked
advertisement



in accordance with 18U.S.C. Section 1734 solely to

indicate this fact.
Requests for reprints:



Sean D. McAllister, California Pacific Medical

Center, Research Institute, 475 Brannan Street, San Francisco, CA
94107. Phone: 415-600-5926; Fax: 415-600-1725.
E-mail: mcallis@cpmcri.org
Copyright



C 2007 American Association for Cancer Research.
doi:10.1158/1535-7163.MCT-07-0371