Shaking out the Dead

K.M. Cholewa: Skin Cancer Awareness Month: What We Know About Cannabinoids and Skin Cancer

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May was Skin Cancer Awareness Month. Here’s some more information from a project I’m collaborating on on the role of cannabinoids in the treatment of cancer.

According to skincancer.org, nearly 5 million people are treated for skin cancer in the U.S. each year, a number which constitutes more cases of skin cancer than the incidence of breast, prostate, lung and colon cancer combined.

There is considerable research on the role cannabinoids can play in the treatment of skin cancer. Consistent findings include that both healthy skin tissue and skin tumors express cannabinoid receptors. Activation of these receptors induce the regression of skin tumors whether through direct apoptosis of cancer cells (self-destruction) or the inhibition of tumor angiogenesis, which is the process by which new blood vessels grow from existing ones, a fundamental step for benign tumors becoming malignant ones. Just as cannabinoid receptors have been found to exist in melanoma cells, melanoma cells also have been found to produce cannabinoids (as well as other bioactive lipids), via the arachidonic acid metabolizing enzymes they express. These cannabinoids, in turn, act on our cells’ CB1 and CB2 receptors. (1)

Given that the growth and development of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) tumors seem to rely on an early burst of neovascularization (2) and that melanoma cells demonstrate a resistance to apoptosis, which makes chemotherapies often ineffective (3), findings demonstrating cannabinoids apoptotic and anti-angiogenetic  properties hold promise for the treating of skin cancer.

Though CB2 receptors have been found to exist in normal human skin and in malignant melanoma, the expression of CB2 receptors is significantly higher in malignant melanoma than healthy skin tissues. (4) Researchers have also looked at the expression of CB2 in sarcoidosis and granuloma annulare, other diseases of the skin. They found that the expression of CB2 was lower in normal tissue than in those diseases, just as they found when comparing normal tissue to malignant melanoma. They concluded that it “may be interred that intensive expression of CB2 in these diseases was related to higher cellular proliferation tendency and aggregation in tissues”and that “CB2 receptor agonists can play an inhibitive role in the origin and development of non-infectious granulomatous disease and tumors by immune regulation.” (5)

In other words, disease and high expression of CB2 receptor was correlated and stimulating activity at the CB2 receptor could generate anti-cancer activity.

Researchers have also experimented with the CB1 receptor, which is the cannabinoid receptor that when stimulated can generate psychoactive results.  A group of researchers from the National Institute of Oncology in Budapest, Hungary reported that two synthetic cannabinoids, one that stimulated the CB1 receptor and one that inhibited it, (Met-F-AEA and AM251, respectably) both  inhibited proliferation of human melanoma cells in lab studies. In fact, CB1 antagonist, AM251, induced massive apoptosis (up to 50%) of human melanoma cell lines. (6)

Another study indicated the role of cannabinoids and the CB1 receptor in inhibiting the migration of melanoma cells to other organs, in addition to the anti-cancer properties mentioned above (promoting apoptosis and inhibiting angiogenesis). In this 2012 mouse study, researchers found that the systemic administration of the synthetic cannabinoid and CB1 agonist, ACEA, “specifically inhibited liver colonization of human melanoma cells.” (7)

Thus, the three hallmarks of the anti-cancer properties of cannabinoids – decreased proliferation and vascularization, increased apoptosis of tumor cells, and inhibition of tumor cell metastatic spreading – have all been demonstrated in skin cancer whether in lab studies, mouse studies, or both. Studies also indicate that cannabinoids create these effects on cancer cells without negatively impacting healthy ones.

More on the anti-cancer properties of cannabinoids here.

1.http://www.aacrmeetingabstracts.org/cgi/content/meeting_abstract/2008/1_Annual_Meeting/2678

2. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC151833/

3. http://www.fasebj.org/content/20/14/2633.full?ijkey=958a31584b617C

4. http://www.res-medical.com/dermatosis-and-std/64093

5. http://www.res-medical.com/dermatosis-and-std/64093

6.http://www.aacrmeetingabstracts.org/cgi/content/meeting_abstract/2008/1_Annual_Meeting/2678

7. http://www.ncbi.nlm.nih.gov/pubmed/22447182

Kate Cholewa author photo

K.M. Cholewa is the author of Shaking Out the Dead. Visit her website for more.

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