Month: February 2009

Boswellic acid (AKBA) and myeloma

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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!

Heart pudding

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I have always had a soft spot for sea otters, amazing little creatures, so, when a blog reader, thanks!, sent me the link to this absolutely charming BBC story: http://tinyurl.com/ajwngw, I thought my heart was going to turn into instant pudding. Check out the second photo….aww, so adorable! Enjoy!

Acronym games: DMAPT/LC-1

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I have had a Google Alert for DMAPT, the parthenolide analogue (see my page on this topic), for ages, now. Whenever I receive a Google Alert on DMAPT, I get all excited, only to discover that it frequently is about a meeting of the Detroit Metropolitan Area Physics Teachers. Aaargh! I am also on a Leukemia and Lymphoma Society alert list for the DMAPT clinical trial, which was supposed to begin months ago in the UK. Until this morning, though, I hadn’t even heard a whisper about the clinical trial that was supposed to begin months ago in the UK.

 

Well, early this morning I discovered why. A blogging friend, Dave, to whom I owe an immense debt of gratitude!, informed me that the acronym DMAPT has been changed to LC-1. You’ve got to be kidding….double-aaargh!

 

Okay, but let’s not get lost in trivial matters, because, guess what?, dramatic drum roll!: the LC-1 clinical trial has begun. Yes indeedie…it began…a few weeks ago…at Cardiff University…in the UK! Hah! I am absolutely delighted, of course.

 

I began doing research immediately, but the more I looked the more I was puzzled. Some sources referred to DMAPT and LC-1 as the same exact thing, whereas others (http://tinyurl.com/dl7go3) called it a novel dimethylamino-parthenolide analogue. An analogue of…an analogue? That made no sense. Moreover, I was left with the doubt that, unlike DMAPT, LC-1 might not attack the leukemic stem cells. I found no mention of this anywhere, you see.

 

So I decided to write to one of the top DMAPT researchers (with whom I corresponded briefly last year), who responded within a few hours in spite of the time difference between the U.S. and Italy. Lovely person, incidentally. Well, it’s simple enough, and I quote from the researcher’s e-mail: LC-1 is simply the commercial designation for DMAPT, they are the same drug. Phew! Relief!

 

The most recent LC-1 news release that I could find is the one that Dave sent to me this morning (the DMAPT researcher sent me the same link, thank you!): http://tinyurl.com/blzqcs As you can see, apart from confirming that the trial has actually begun!, the main titbit is that so far LC-1 has been well tolerated by the patients in the study. Good!

 

Note: LC-1 is not a new acronym, by the way (how could I have missed that??? Dear, dear…). I came across this “Molecular Cancer Therapeutics” study that was published in 2007: http://tinyurl.com/ctuzj8. LC-1 was tested, successfully, together with Sulindac, a COX inhibitor, against pancreatic cancer in vitro and in vivo (= mice).

 

Well, we will just have to be sit back and be patient for a while…but you can rest assured that I will change my Google Alert…! Che roba!

Inhibiting IL-1 beta through diet

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The list of plant extracts and foods that inhibit IL-1 beta is overwhelming, even more so when you consider that it is composed only of the items that I have been able to think of and look up thus far, in my snippets of time…how many more are there?!

 

The following, therefore, is probably only a partial list of foods (and/or their compounds) that inhibit IL-1 beta. It is intended mainly for those who don’t take supplements for one reason or another. I should note that I frequently found more than just one study per food/food compound:

 

Garlic: http://tinyurl.com/aae5n6

 

Possibly capsaicin: http://tinyurl.com/csjhqu It is the active ingredient in hot chili peppers and has anti-myeloma activity (see my page on capsaicin)

 

Ginger extract: http://tinyurl.com/cqv9f7 (also anti-myeloma, see my ginger page)

 

Ursolic acid: http://tinyurl.com/bn86pr  Found mainly in: rosemary, apples, bilberries, cranberries, pears, peppermint, lavender, oregano, holy basil, thyme and prunes (see my page on the anti-myeloma effects of ursolic acid, which inhibits STAT3).

 

Olive oil: http://tinyurl.com/begrvy

 

Blueberries: http://tinyurl.com/bm3zsz  

 

White wine (compounds): http://tinyurl.com/dby9jf

 

Xanthohumol: http://tinyurl.com/dc8kvg Found in beer.

 

Caffeic acid: http://tinyurl.com/b64y2s Found in many fruits, vegetables and herbs. Also in, drum roll!, coffee!

 

Grapes and grape extract: http://tinyurl.com/bzk7rh

 

Anything from the Brassicaceae family (= broccoli, cabbage…): http://tinyurl.com/aw2f8h

 

And finally, we should eat truckloads of artichokes, which contain silymarin, an active compound in milk thistle and IL-1 beta inhibitor: http://tinyurl.com/bpyzqj  

 

More to come…

EGCG blocks Velcade

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My thanks today go to a blog reader who sent me this link to a February 3 2009 “Blood” abstract: http://tinyurl.com/c9ppr2 Even though I haven’t accessed the full study yet (but hope to do so soon), the abstract provides enough information to determine that if you are on Velcade (bortezomib) or any other boronic acid-based proteasome inhibitor, you shouldn’t even look sideways at a cup of green tea, let alone drink it.

 

A team of University of Southern California researchers discovered, in fact, that many of the substances contained in green tea, in particular EGCG, effectively prevented tumor cell death induced by bortezomib in vitro and in vivo. In plainer words: when used in the presence of EGCG and other green tea components, Velcade could not kill off any myeloma cells. So today I have a warning: if you are currently taking Velcade, please do not drink any green tea or take any supplements containing EGCG.

Of course, if you are not on bortezomib, well then, that’s another…cup of tea.

P.S. In August 2008, I posted about a “Blood” study on flavonoids and Velcade, please scroll down my Pages to “Dietary flavonoids and Bortezomib” (under “Related Topics”). A curious study, I must say. If you are a CLL patient on Velcade, for instance, you should not take any quercetin. If, however, you are a myeloma patient on Velcade, quercetin can help prime the myeloma cells to the killing effect of this drug. The flavonoid puzzle…

IL-1beta involved in progression from inactive to active myeloma

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I found out about this wonderful little gem from a couple of myeloma list friends (thank you both so very much, D & D!). It’s an editorial (see: http://tinyurl.com/b7z59z) on a Mayo Clinic study titled “Targeting the Pathogenic Role of Interleukin 1beta in the Progression of Smoldering/Indolent Myeloma to Active Disease,” (abstract: http://tinyurl.com/acqlkb; full study: http://tinyurl.com/akqd4r). I haven’t read the full study yet (I will read it tomorrow…it requires more attention and care than I can give it at the moment: ). Both can be found in the February 2009 Mayo Clinic Proceedings. At any rate, I am basing my post on the editorial (shorter and easier to read than the full study…).

 

47 patients, all at the inactive or smouldering myeloma stage (=my stage) but at high risk of progression, participated in the Mayo study, which was carried out between 2002 and 2007. The idea was to answer the fundamental question: WHAT THE HECK makes folks progress from inactive to active myeloma?

 

Apparently what happens is that IL-1beta, another of those beastly pro-inflammatory and pro-angiogenic cytokines, induces marrow stromal cells to produce large amounts of interleukin 6 (IL-6), thereby promoting the survival and expansion of the myeloma cells. 

 

The researchers confirmed their theory that reducing the activity of IL-1beta does, in fact, significantly increase progression-free survival (PFS) in these high-risk patients. This is extraordinary!

 

And now read this: blocking IL-1beta reduces IL-6 as well as the proangiogenic chemokine IL-8, therefore the use of IL-1beta-blocking strategies may result in new standards of therapy for high-risk patients with SMM/IMM. WOWIE!!!

 

In the study, all the smouldering myeloma patients were given anakinra, an IL-1beta inhibitor that is used for the treatment of rheumatoid arthritis and autoinflammatory diseases. I should add that 25 patients were also given a low dose of dexamethasone. Two of the them remained stable for about four years, and in fact, at the time of this writing, progression to active disease has not yet occurred […]. Since, as I mentioned, I haven’t yet read the actual study, I don’t know what happened in the other 23 cases…

 

Another significant excerpt from the editorial: In the study, patients with a decrease in CRP levels were more likely to have stable disease, confirming that effectively blocking IL-1beta (using CRP levels as the marker for IL-1beta activity) can halt progression to active myeloma.

 

Halt progression to active myeloma…aaaaah, how sweet those five little words sound…

 

Hmmm, but WHY am I so excited that I could skip and dance all around my study (probably will, as soon as I post this)?

 

Because, drum roll!, CURCUMIN INHIBITS IL-1BETA!!! (See, e.g.: http://tinyurl.com/b7yr3j and http://tinyurl.com/bgqud4) There are heaps of studies on this topic, in fact, probably much much better than the above two that I found after a lightning search…but right now I am too elated and, well, in a bit of a hurry–it’s almost dinnertime–to see if I can find the perfect one…I just want to go ahead and post this bit of good news!

 

More good news: curcumin is not the only one. Here is a list of the other natural IL-1beta inhibitors that I have found thus far (ah, but my quest has only just begun, so there will probably be more…):

 

1.     quercetin (strongly) http://tinyurl.com/dfy39r and http://tinyurl.com/c6v3np

2.     omega-3 http://tinyurl.com/c2ksmg

3.     genistein http://tinyurl.com/cbtpsr

4.     EGCG http://tinyurl.com/andmdj

5.     resveratrol http://tinyurl.com/cmnayw

6.     ellagic acid (on my to-be-tested list) http://tinyurl.com/bgvutf

 

I will stop here because I want to go give my husband a big bear hug…and do another little jig of joy around the room on the way! Yippity yippity doodle! Evvaiiiii, grandeeeee!!! 🙂