NF-kB: Dr. Jekyll or Mr. Hyde?

A blog reader and I recently had an interesting exchange about this transcription factor, which is so important in myeloma…in a negative sense, unfortunately. Our discussion gave me the incentive to read more about it. My good friend Sherlock (grazie!) sent me a study published in January (2008) in “Experimental Biology and Medicine,” titled “Nuclear Factor-kB Activation: From Bench to Bedside,” and co-authored by Prof. B. Aggarwal (abstract:

This transcription factor, discovered in 1986, was called NF-kB “because it was found in the nucleus bound to an enhancer element of the immunoglobulin kappa light chain gene in B cells.” Okay, wrap your brain around that!  But seriously, if you reread the quote slowly, it begins to make sense: it’s a thingie (protein complex or transcription factor) sticking to the “kappa” gene inside a B cell’s nucleus.

Under normal circumstances, our immune system needs NF-kB to fight off diseases and infections. And until it is needed, this transcription factor follows my cats’ example and takes a lot of very long naps. I don’t want to go into its mechanisms of action (complicated stuff!), at least not today. Let it suffice that, once it has accomplished its task, it settles back down for another nap.

The study informs us that NF-kB is present in every type of cell, not just B cells as was first thought. Researchers have in fact discovered that it is located in the cytoplasm (the watery environment surrounding the cell nucleus) of all types of animal (from the fruit fly to us) cells. Another important finding is that it moves, or translocates, to the cell nucleus only when activated. Otherwise, it stays in, or (once it has finished its task) goes back to, the cytoplasm.

Things change with cancer. That’s when NF-kB turns into Mr. Hyde: it goes bonkers for a variety of reasons and ends up being active ALL the time, or constitutively active. And when this happens, NF-kB remains inside the cell nucleus, that is, it doesn’t return to the cytoplasm. No more naptime!

Skipping the technical parts about heterodimers, polyubiquitination and nuclear localization sequences (!), let me get to what we are really interested in: how does this transcription factor get activated in cancer cells? The study provides an answer: “NF-kB is activated by many divergent stimuli, including proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), epidermal growth factor (EGF), T- and B-cell mitogens, bacteria and lipopolysaccharides (LPS), viruses, viral proteins, double-stranded RNA, and physical and chemical stresses.” Radiation and chemotherapy also activate NF-kB. Speaking of which, the study tells us also that "Cells that express constitutively activated NF-kB are resistant to various chemotherapeutic agents and radiation treatment.” Vicious circle?

Another key sentence: “In tumor cells, different types of molecular alterations may result in impaired regulation of NF-kB activation. In such cases, NF-kB loses its transient nature of activation and becomes constitutively activated. This leads to deregulated expression of NF-kB– controlled genes.” NF-kB, the study continues, plays a critical role in cancer cell survival, inflammation, growth and so on. It regulates genes that are implicated in cancer cell proliferation, including TNF-alpha, IL-6, to name just a couple that we know are essential growth factors in multiple myeloma. It also regulates some of the cell cycle-regulatory proteins such as cyclin D1, also involved in myeloma (see my page on Ursolic Acid or my December 4 2007 post for more info on this gene, which has recently been associated with disease activity and progression).

Activated NF-kB is also implicated in the control of anti-apoptotic genes, that is, genes that keep cancer cells healthy and alive, such as survivin and Bcl-2 (again, see my post on ursolic acid). Furthermore, it regulates matrix metalloproteinases, or MMPs, which are proteases (protein-dissolving enzymes) that, among other things, promote cancer cell growth and angiogenesis. Okay, so there is no question that constitutively active NF-kB is not a good thing.

That’s enough for today, but I would like to end with a question: if we systemically inhibit NF-kB in order to stop our cancer from progressing, doesn’t that leave us more susceptible to infections? (More on this topic SOON!)


  1. Hi Margaret

    How well you explain everthing, thank you fro putting it into understandable english. You’ll be able to pass 2 or 3 degrees by the time you’ve finished!!
    By the way I have just seen on an American web page that New Chapter do a pure Baikal Scullcap and also a product called Headache relief (this one contains amongst other things Feverfew(Parthenolide)). Trying to find out if it’s available in England. Haven’t had any luck so far, does anyone know.


  2. Have you seen Dr. Aggarwal’s powerpoint demonstration relating to NF-kB, at ? It’s interesting to me because it shows the association of autoimmune problems to cancer (or MGUS) via NF-kB. I guess this explains why there is such a close association between cancer and autoimmune disease, and why sometimes when cancer is beat the autoimmune disease also disappears.

  3. Please Please can someone help me. I live in the UK and have an uncle who Myeloma. He has regular transfusions etc etc but is getting weaker as he has lost his appetite. He says that when he sees food he feels sick. Is there anything anyone can suggest that I can get for him here to help hom deal with thsi problem

  4. Hi Gerard,
    Sometimes when things aren’t going well you have to take a gamble. One website I came across referred to a German doctor called Johanna Budwig who appears to have had success with seriously ill patients by feeding them flaxseed oil and quark or live yoghurt. (see:
    You might also ask the doctor about your uncle’s blood calcium level and kidney function.
    Good luck,

  5. Hi Gerard, as Paul wisely pointed out, lack of appetite and nausea can be caused by too much calcium being released into the bloodstream (it’s called hypercalcaemia) and perhaps problems related to kidney function. I would certainly ask the doctors about those tests in particular. Sometimes the chemotherapy treatments can also cause those kinds of side effects.

    I don’t know much about the Budwig diet, but it does seem to work in many cases. If your uncle could bring himself to eat some yoghurt, well, why not?

    My best advice is to ask his doctors and try to find the best solution together with them. Sorry not to be of further help.

    Take good care,

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