IGF-1, the American mayapple, curcumin and multiple myeloma. Part II

First, I searched PubMed to see if curcumin possibly inhibits this growth hormone that has such a negative impact on myeloma patients. Hah. Quelle surprise! It does! So curcumin-takers are a step ahead, it would seem. Here are the two main studies:

  1. A 2008 study on colon cancer cells, chemo and curcumin (see: http://tinyurl.com/yajdk5s) found that the superior effects of the combination therapy of curcumin and FOLFOX are due to attenuation of EGFRs and IGF-1R signaling pathways. We also suggest that inclusion of curcumin to the conventional chemotherapeutic agent(s)/regimen could be an effective therapeutic strategy for colorectal cancer. (FOLFOX, btw, is a chemo regimen for patients with colorectal cancer.)
  2. A 2007 breast cancer cell (=MCF-7) study showed that curcumin exhibited a potent ability to blunt IGF-1-stimulated MCF-7 cell growth and reverse the IGF-1-induced apoptosis resistance. See: http://tinyurl.com/ye3jqje

I then checked out some of the other anti-myeloma, non toxic substances discussed on my blog. Bingo, again. Here is just a sampling of what I found:

  • 2009 study on resveratrol and genistein: Polyphenol treatments decreased cell proliferation and insulin-like growth factor-1 (IGF-1) protein expression in the prostate, see http://tinyurl.com/yesbb5q
  • 2008 study (see: http://tinyurl.com/yea69yn): resveratrol significantly inhibited IGF-1 in breast cancer cells.
  • The 2008 myeloma-parthenolide study that I posted about on June 4 2008 (see my Page on parthenolide or click here for the full study: http://tinyurl.com/ydousu2) shows that parthenolide, extracted from the feverfew plant, overcame the proliferative effects of cytokines interleukin-6 and insulin-like growth factor I, whereas the adhesion of MM cells to bone marrow stromal cells partially protected MM cells against parthenolide effect. (Blasted adhesion!)
  • 2009, prostate cancer-EGCG study (see: http://tinyurl.com/ydkbgw3). EGCG decreased the levels of IGF-1 (as well as having other beneficial effects). Same thing for colorectal cancer, see http://tinyurl.com/yat8wjt .

This post could easily turn into a long boring laundry list, so I will stop here. However, if you want to find out if any of the supplements that you are taking might inhibit IGF-1, just go to PubMed (general link: http://www.ncbi.nlm.nih.gov/) and type in your key words. Easy peasy.

Let’s move on. I would like now to discuss a Science Daily article that I read in September: http://tinyurl.com/ydxxcgm It gives us an overview of podophyllotoxin, an anticancer compound extracted from the roots and rhizomes of an endangered Indian medicinal plant but also from those of the common American mayapple (for an overview of this plant: http://tinyurl.com/yccs83x). This compound, incidentally, is found in the chemo drug etoposide, used to treat lymphoblastic leukemia, brain tumours and other types of cancer. The abstract of the study discussed in the SD article can be found here: http://tinyurl.com/nh4grx

As usual, I checked PubMed, where I found that picropodophyllin was tested in 2007 against myeloma cells, too. Hah! And, double hah!, the full study is available online: http://tinyurl.com/y8p4nzh The results are astounding: targeting the IGF-1R using picropodophyllin (PPP) in a therapeutical setting not only has strong antitumor activity on the established MM tumor but also influences the BM microenvironment by inhibiting angiogenesis and bone disease, having a profound effect on the survival of the mice. Wowie.

An important point: this study tested the impact of PPP in models of established myeloma, that is, not just on MM cells. They used what is called the 5T2MM mouse model, representing an in vivo model of established, slow growing myeloma. Now, you can read the details on your own (the study isn’t a difficult one compared to others I have encountered!), but let me give you just a few interesting results:

  1. PPP significantly reduced the tumor burden in the 5T2MM model. Up to 75% reduction in serum paraprotein.
  2. PPP reduced the accumulation of myeloma cells in the spleen by 70%.
  3. Mice treated with PPP survived 180 days…compared to the 100 days of the untreated ones.
  4. PPP also inhibits angiogenesis (good news for us).
  5. PPP may have a direct effect on osteoclast formation and osteolysis. It inhibits osteolytic lesions, a colossal problem in myeloma, as we know.
  6. The study concludes that blocking IGF-1R signaling with the receptor inhibitor PPP not only has a strong antitumoral effect in MM but also has a significant impact on the BM microenvironment, a key contributor to MM tumor expansion.

Let me point out that there are a couple of previous studies on the myeloma-picropodophyllin issue: a 2006 study (full text: http://tinyurl.com/yakrvy6) that I haven’t had the time to read yet, but that concludes that PPP targets the IGF-1RTK, blocks the IGF-1R function in vitro and in vivo, reduces tumor burden, and is associated with prolonged survival and this in the absence of apparent in vivo toxicity

The same edition of “Blood” has a study by the same group of researchers (full text: http://tinyurl.com/ydcqfl8), which comes to the same conclusions. I would like to highlight that PPP also decreased the levels of survivin and mcl-1, among other things.

I have more (strong) thoughts on this topic, but that is fodder for a separate post. Stay tuned!


  1. Thanks Margaret for your diligent research. You provide our myeloma community with many interesting ideas. At the clinic where I was treated, one of the chemo drugs for the pre-transplant protocol included etoposide, mentioned above.

  2. In July, you had a link to an abstract about a study about MM and saw palmetto (Serenoa repens). IGF-1 was not mentioned in the abstract, although I believe inhibition of IL-6 was.

    So, I used the PubMed link you provided today, and did a search using the terms IGF-1 and “saw palmetto”. Here is what came out:

    “1: Endocrinology. 2004 Jul;145(7):3205-14. Epub 2004 Mar 19.

    Saw palmetto extract suppresses insulin-like growth factor-I signaling and induces stress-activated protein kinase/c-Jun N-terminal kinase phosphorylation in human prostate epithelial cells.”

    Now, this study was not done on MM cells, but if it has this effect on prostate epithelial cells, it seems quite possible it would also on MM cells. Not only that, but it sounds to me that S. repens also activates a protein (JNK) which induces cell apoptosis.

    If you can get hold of the complete study you mentioned in July, it would be interesting to see whether they tested for effects of saw palmetto on IGF-1, and what those results were.

Leave a Reply

Your email address will not be published. Required fields are marked *