A blogging friend sent me the full genistein study (thanks!!!) recently published in “Phytotherapy Research” (abstract: http://tinyurl.com/7wwnku), a study that I mentioned in my December 29th post. It starts out with the usual dismal information about multiple myeloma, which is a B-cell malignancy characterized by the latent accumulation in bone marrow of secretory plasma cells with a low proliferative index and an extended life span and accounts for 1% of all cancers and more than 10% of all blood cancers…oh, and it remains incurable…
There follows a description of what happens when the transcription factor NF-kappaB gets constitutively activated (that simply means that it is activated all the time)…this is not good, as far as we myeloma folks are concerned, since it means that our myeloma cells are protected from apoptosis (=from kicking the bucket). Reading on…blablablabla…okay, the upshot: NF-kappaB is an important target for myeloma treatment. So far, we have learned nothing new.
The research team chose to test genistein, a predominant isoflavone found in soybeans, which has been shown to inhibit the growth of various cancer cells in vitro and in vivo without toxicity to normal cells. Genistein suppresses NF-kappaB and many of the genes that it regulates. And humans can consume it safely, so they say.
Results. The team tested two different myeloma cell lines that expressed a hyperactive NF-kappaB. The cells were treated with different amounts of genistein and doxorubicin. A very small amount of genistein was sufficient to suppress the activation of NF-kappaB. It also worked synergistically with doxorubicin, leading to greater antitumor activity in vitro. Good.
For the more technically-oriented, genistein also inhibited Akt phosphorylation (when this happens, NF-kappaB doesn’t travel to the nucleus, which is a GOOD thing, take my word for it) and down-regulated ICAM-1, cyclin D, bcl-2 and bcl-xL (=four wicked genes).
Okay, but does genistein kill myeloma cells? Yes. How? Well, The precise molecular mechanism is not clear, the researchers admit. But wowie zowie, check this out: like curcumin, zerumbone and cyclopamine, genistein inhibits the Notch-1 pathway…does anyone remember what that pathway is? Right, it has to do with STEM cells…well, this might tip the balance in genistein’s favour, as far as I am concerned…yes, this is good news indeedie! I am so glad I read the full study!
Thanks to my big-hearted blogging friend, I have in my possession the 2006 genistein-Notch full study, which is next on my reading list…in the meantime, scribble scribble, a mental note: make more chickpea curries for dinner…
Why the chickpea curry? Do chickpeas have genestein?
I’ve been making curries with baked tofu squares trying to gather up the goodness of tumeric and soy.
A pubmed study discussing synergy between genistein and gossypol :
Nonpeptidic small-molecule inhibitor of Bcl-2 and Bcl-XL, (-)-Gossypol, enhances biological effect of genistein against BxPC-3 human pancreatic cancer cell line.Mohammad RM, Wang S, Banerjee S, Wu X, Chen J, Sarkar FH.
Division of Hematology and Oncology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI 48201, USA. Mohammad@karmanos.org
OBJECTIVES: In pancreatic cancer, several important survival molecules such as EGFR, NF-kappaB, and Bcl-2 or Bcl-XL are highly activated. Thus, agents that inhibit NF-kappaB activation, together with agents that directly inhibit Bcl-2 or Bcl-XL protein function, may lead to enhanced cell killing. (-)-Gossypol, a natural polyphenolic compound isolated from cottonseeds, is a dual and potent small-molecule inhibitor of Bcl-2 and Bcl-XL proteins, with a Ki value in the 300-600 nM range for both proteins. METHODS:: The BxPC-3 human pancreatic cell line was used in this study. (-)-Gossypol was dissolved in DMSO at 20 mmol/L as stock solution, and genistein was dissolved in 0.1 M Na2CO3 to make a 10 mM stock solution. For cell viability, apoptosis, and NF-kappaB studies, MTT assay, histone/DNA ELISA, and Electrophoretic Mobility Shift Assay (EMSA) were used, respectively. Coimmunoprecipitation experiments were designed to study Bcl-XL/Bim heterodimerization, and Western blots to study cytochrome c release. RESULTS: (-)-Gossypol showed a concentration-dependent growth inhibition effect against BxPC-3 pancreatic cancer cell line and induced apoptosis with no effect on normal peripheral blood lymphocytes. Results from coimmunoprecipitation experiments indicate that the effect of (-)-gossypol is mediated, at least, in part via disrupting the heterodimerization of Bcl-XL with Bim in BxPC-3 pancreatic cancer cells. (-)-Gossypol completely disrupts Bcl-XL/Bim heterodimerization with no change in the total Bcl-XL or Bim protein, indicating that (-)-gossypol treatment does not affect the levels of Bcl-XL and Bim proteins. We have previously shown that genistein, a prominent soy isoflavone, transcriptionally down-regulates Bcl-2, Bcl-XL, VEGF, MMP-9, and uPAR via inhibiting NF-kappaB activity. In this study, genistein down-regulated NF-kappaB DNA binding activity and inhibited the growth of BxPC-3 pancreatic cancer cells. In addition, the combination of (-)-gossypol with genistein showed significantly greater growth inhibition compared with either agent alone. CONCLUSION: From these results, we conclude that inhibition of NF-kappaB activity and direct inhibition of Bcl-2 or Bcl-XL function should serve as a novel strategy for pancreatic cancer therapy.
Thanks, Art, I will update my genistein and gossypol pages. Too bad that gossypol is a bit on the toxic side, eh…
Margaret
I’ve been taking genistein for a while, because (a) it improves the bioavailability of curcumin and (b) it’s effective against prostate cancer as well as multiple myeloma. I’ve been taking it in the form of red clover capsules. The problem is that red clover contains only a minute amount of genistein. Now I’ve bought the most powerful genistein on the general market: Quality AHCC GeniKinoko 335 mg capsules of Genistein Combined Polysaccharids (GCP). The disadvantage is the price: $US 284.50 for 180 capsules (at 6 capsules a day, that’s one month’s supply!). I’ll take them for a month before my next blood test, and see what they do to my PSA.
– Alex