One of the crucial myeloma survival pathways is called STAT3. The importance of this protein in myeloma is nothing new…I have already mentioned it here and there (see, e.g., my page on ursolic acid). I have also been collecting data on STAT3 for some time and will soon write a post about it. Just quickly, though, when STAT3 goes bonkers (for reasons that we will see in my future post), myeloma cells are able to survive and proliferate. The same occurs in many other types of cancer: prostate, brain, pancreatic and breast cancers, just to mention a few.  

Today I want to concentrate on a January 2009 study published in “Molecular Cancer Research” (one of the co-authors is Prof. Aggarwal, quelle surprise!). It examines the anti-myeloma effects of one of the boswellic acids, “acetyl-keto-beta-boswellic acid” or AKBA, which can be found in the gummy resin of Boswellia serrata, also known as Indian frankincense. Like so many other wonderful herbs and plant extracts, this resin has been used for centuries in Ayurvedic medicine to treat a variety of ailments, in particular those linked to inflammation: arthritis, bursitis and asthma, e.g. See these 2003 and 2008 osteoarthritis studies: http://tinyurl.com/c9z88t and http://tinyurl.com/dc6gbq

A blogging friend (thanks!) sent me the full 2009 AKBA-myeloma study (abstract: http://tinyurl.com/bry5ua)

I first checked to see if boswellic acid could block IL-1 beta, but alas, I found nothing. I don’t give up easily, so I checked elsewhere. Success! A 2006 “Journal of Immunology” study (again, co-authored by Prof. Aggarwal) shows that AKBA inhibits all sorts of evil stuff, including NF-kappaB and, aha!, IL-1 beta: http://tinyurl.com/cr23qe

Oh, and guess what? This 2006 study tells us that boswellic acid also inhibits osteoclastogenesis, a huge concern for us myeloma folks. (That means that it stops the process of bone destruction.) All excellent news.

Let’s get back to the 2009 myeloma-boswellic acid study. As we can read in the abstract, the researchers found that boswellic acid blocked IL-6’s activation of the STAT3 pathway. By inhibiting STAT3, other evil thingies that cause myeloma cells to proliferate and survive were also stopped dead in their tracks, such as cyclin D1, survivin and the Bcl family members (see previous posts). As a result, with all their survival mechanisms cut off, myeloma cells had no choice but to jump off a steep cliff…without a parachute.

Speaking of jumping, let’s jump into the full study. It begins with an important statement: Numerous recent reports indicate that multitargeted, rather than monotargeted, anticancer agents have a better chance for success. Most natural products are multitargeted ‘‘naturally’’. Boswellia serrata, an Indian frankincense or Salai guggul, has been used in Ayurvedic systems of medicine against a number of inflammatory diseases, including osteoarthritis, chronic colitis, ulcerative colitis, Crohn’s disease and bronchial asthma but the mechanism is poorly understood. By the way, all the scientifically-backed anti-myeloma (and anticancer) substances listed on my blog are multi-targeted…

The following paragraph is for the more technically-inclined: AKBA inhibits constitutive STAT3 phosphorylation (a process that was found to be reversible, when the compound was removed), IL-6-induced STAT3 phosphorylation and the constitutive activation of JAK2. It also suppresses the nuclear translocation of STAT3, inhibites the binding of STAT3 to the DNA and angiogenesis (VEGF). It also blocks COX-2 and can suppress the growth of glioma, colon cancer, prostate, and leukemic cells. The inhibition list goes on and on and on. Extraordinary…

I had already read good things about boswellic acid, but I hadn’t given it much serious thought because I hadn’t (until now) read any scientific studies on its anti-myeloma effects. An excerpt from the Discussion confirms that this is the first study on AKBA’s anti-myeloma effects: Because STAT3 has been linked with survival, proliferation, chemoresistance, and angiogenesis of tumor cells, its inhibitors have potential for the treatment of cancer. In the present study, we report the identification of a novel inhibitor of STAT3. We found that AKBA inhibited both constitutive and IL-6–induced STAT3 activation in MM cells […].This is the first report to suggest that AKBA can inhibit STAT3 activation.

In conclusion, we now have another extremely valid item to add to our ever-increasing and rather impressive collection of anti-myeloma non-toxic substances. I will have to try it!