Any time something related to a
medical use for cannabis is found, it
makes headlines. Mostly, the interest is generated by the
relationship to an illegal drug. Sometimes, though, the media
do a decent job of reporting the real issue.
at the California
Pacific Medical Center Research Institute
have announced that one of the compounds found in cannabis,
inhibits a gene that is important for the growth and metastasis of
Note that this has nothing to do with medical marijuana, really.
Cannabidiol is not psychoactive: it does not produce
euphoria. Moreover, it is not possible to get enough into
your body by smoking cannabis.
This has been reported by the
and others. Most of the reporting is good, although there is
one glaring error in the Washington Post article (I’ll get to that).
The action is centered upon a pair of genes that are
involved in the
regulation of cell growth. Both genes code for proteins that
are essential for normal growth. However, when growth is not
regulated normally, it can get out of control. The result may
be the development of a malignant tumor that can spread to various
other body sites. If the expression of the genes is not
properly regulated, then the proteins they encode are produced in
unhealthy amounts. Thus, the regulation of gene expression is
crucial for the proper regulation of cell growth.
The researchers involved in the studies included href="http://www.cpmc.org/professionals/research/programs/science/sean.html"
rel="tag">Sean McAllister, Ph.D., and href="http://www.cpmc.org/professionals/research/programs/science/desprez.html"
rel="tag">Pierre Desprez, Ph.D.
They have been studying two genes:
of DNA binding-1 (Id-1), and href="http://www.cbcrp.org/research/PageGrant.asp?grant_id=2038">inhibitor
of DNA binding-2 (Id-2). In general, Id proteins
tend to stop the differentiation of cells, and promote cell division.
The do this by regulating transcription factors.
The CPMCRI researchers report that, in cultures of mouse breast cancer
cells, the two proteins have opposite effects. href="http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=16469432&ordinalpos=5&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum">Id-1
tends to promote proliferation of the cells, whereas href="http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=15688367&ordinalpos=5&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum">Id-2
tends to restrain breast cancer cell proliferation.
What Desprez and McAllister found is that cannabidiol suppresses the
Id-1 gene. This results in lower levels of the associated
protein, which in turn results in less tumor growth and less
Obviously, this is all very preliminary. The work so far has
been done with cultured mouse cells. That is a lot different
than cells in a live human. The news articles were careful to
point that out.
The Washington Post article, however, contains an odd statement:
In humans, the Id-1 gene is found only in
metastatic cancer cells, said Desprez, a staff scientist at the
institute. Before birth, they are present and involved in the
development of human embryos, but after birth, they go silent — and
should stay that way, he said.
I don’t think Desprez said that. Rather, the reporter
(Carolyn Colwell) inferred that from something else. I don’t
think the gene simply disappears and then comes back. Rather,
the protein that the gene encodes is what comes and goes.
When the gene is silent, the protein goes away.
When the gene is turned back on, the protein comes back.
This point is peripheral to the main points in the
article. I don’t blame the reporter (too much), because it is
a complex subject. It is easy to get confused. But
I don’t want to perpetuate the confusion by failing to point this out.
The results of the research have been published in the journal, Molecular
as a novel inhibitor of Id-1 gene expression in aggressive breast
Molecular Cancer Therapeutics
6, 2921-2927, November 1, 2007.
Sean D. McAllister, Rigel T.,
Maxx P. Horowitz, Amaiaand
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]
Note especially that the authors state that CBD inhibits the
proliferation of the cells, makes tham less invasive, and makes them
less aggressive. They do not say anything about a cure.
On the CPMCRI website, they do not say that
they expect CBD to be useful clinically. Rather, they say
that it may serve as a template for other compounds that might turn out
to be clinically useful.
Looking at the Medline database, these researchers have been at this
for at least ten years already, just to get to this point. I
won’t even try to guess how long it may be before anything clinically
useful may come of it. Even so, it is exciting to see a
prospect for a safe drug that may have little or none of the
unpleasantness that is so troublesome in so many anticancer drugs.