Article Title: Genistein...The Cure For Platinum Resistance?
Introduction 
Soy has been promoted as a super health food, yet many do not know that it is 'fermented' soy that yields the most health benefits including cancer treatment and prevention. It is well known that countries with the highest consumption of fermented soy, have the lowest rates of cancer. Two components which are in great quantity in fermented soy are Genistein and Daidzein, both of which are showing promise in cancer research.
Genistein is an plant produced isoflavone (5,7,4'-trihydroxyisoflavone),which becomes a phytoestrogen in mammals12. This means it is a weak estrogen (about 1/500th the amount of a normal human estorgen13). For this reason it is known as an antiestorgen in animal models7 by attaching itself to the estrogen (oestrogen) receptors of cells, it can be used to interfere with estrogen receptive cancers.
Genistein has been studied extensively and shown in vitro and in vivo to be cytotoxic (anti-neoplastic) and chemosensitizing to human ovarian cancer cells.1 It has so much promise that the Marshall Edwards company out of Australia has developed an analog of genistein into a chemotherapy drug called Phenoxodiol (2H-1-benzopyran-7-0,3(hydroxlyphnyl) which is currently in Phase III clinical trials. Phenoxodiol has shown success on it's own (monotheraphy) but with even greater success when used with chemotherapy.2
What does Genistein do to Ovarian Cancer cells?
Researchers have discovered the following in realtion to ovarian cancer cells and genistein:
- Causes Apoptosis (programmed cell death) and Autophagocytosis (cellular degradation11) of cancer cells1. Most current chemotheraputic agents only induce apopotic cell death
- Is anti-neoplastic to ovarian cancer cells1,6,15
- Phenoxodiol interacts with tNOX (tNOX 75 Alpha to be specific) to help prevent cancer growth.2 tNOX appears on the surface of cancer cells (normal cells only have 'NOX') and is believed to promote agressive cell multiplication (tumor growth and development)3. For example, green tea is yet another natural source that interacts with tNOX4 and is possibly one reason it helps combat ovarian cancer.
- Dramatically inhibits glucose uptake in ovarian cancer cells1,15. It is well known that glucose (sugar) is consumed by cancer cells more than normal cells5.
- Inhibition of tyrosine kinase activation (an EGF - Epidermal Growth Factor - receptor) which enhances aerobic glycolysis in cancer cells15. It is believed that tyrosine kinase contributes to the inhibition of apoptosis and promotes chemoresistance in ovarian cancer cells. Genistein is believed to reverse this.15 Src family Tyrosine Kinase is overly expressed in ovarian cancer cells and inhibiting it, along with using a chemotherapy drug like Taxol, activates a cell-killing pathyway involving caspase-316.
- Stabilizes and/or reduces CA-125 levels6
- Is not toxic to normal cells6
- Potentially interferes with the CXCR4/CXCL12 axis which is known to assist with the metastasis of breast cancer and the development of ovarian cancer. When combined with DIM (diindolylmethane), the CXCR4 and CXCL12 are reduced to that of normal cells.8 CXCR4 has been shown to be active in the ovarian cancer cell line OC 314 which assists Epidermal Growth Factor (EGF) Receptor Transactivation 10.
- When combined with DIM (in vitro), effectively halts ovarian cancer cells. When used alone, significantly slows them.8
Genistein for Treating Ovarian Cancer
Based on the mounting evidence and research, it looks like Genistein has a true place in Ovarian Cancer treatment. But how do you go about using it? The following is not intended as medical advice, you should consult with your oncologist:
- Ask your oncologist to find a Phenoxodiol trial for you. Currently this is called the OVATURE trial (Phase III): http://www.marshalledwardsinc.com/index11.cfm?section=11. Phenoxodiol is an analog of Genistein that has been developed to be more powerful and selective than the natural occuring form. They are testing out both intravenous (IV) and oral versions. The current trials use oral versions (tablets) along with weekly platinum based treatments (which have been shown in 2001 by researchers in Denmark to be effective on their own for platinum resistant ovarian cancer).
- Supplements and Fermented Soy: The current research by UCLA (the most recent research on Genistein that has been published as of this article date), stated that the amount they used would be comparable to a use of high dose supplements8. We do know that one woman who used a fermented soy beverage (Haelan 951, 4oz bottle per day) which has high amounts of Genistein to stabalize her CA-125 levels (and subsequently make her platinum resistant ovarian cancer sensitive again). The research showed that Haelan 951 has about 30.5mg of Genistein and 15.1mg of Daidzein in a 4oz bottle6. So that is the only current 'benchmark' that I know of that has been researched in an in vivo case.
You will need to shop around for what supplement you feel best with. For example, Life Extension has what appears to be a good bioavailable version here: http://www.lef.org/newshop/items/item00758.html
Using Haelan 951 may not appeal to many western patients as it is not an appealing drink (hey, it's fermented soy!) and it is expensive. You can view research on their products and cancer here: http://www.haelanresearchfoundation.com/research.html
Conclusion
While there is sufficient research on the power of Genistein and ovarian cancer, there is unlikely to be any FDA clinical trials with any supplement versions of Genistein because of the immense cost to produce a clinical trial. Therefore one can only base the available in vitro research along with any in vivo research that comes across. Phenoxodiol, when approved (it's on the FDA fast track), should be an effective solution for those with any stage ovarian cancer but it is currently only in FDA Phase III trials that (as of 2007) have only just begun in the United States. If one wishes to use supplementation of Genistein with their current treatment of ovarian cancer, it is recommended they talk about this with their oncologist (be sure to bring citations and references to assist them if they are not aware of this research) about the possible advantages or disadvantages of using Genistein and the current chemotherapy drug(s).
Disclaimer
The information provided on this site is for informational purposes only and is not intended as a substitute for advice from your physician or other health care professional or any information contained on or in any product label or packaging. You should not use the information on this site for diagnosis or treatment of any health problem or for prescription of any medication or other treatment. You should consult with a healthcare professional before starting any diet, exercise or supplementation program, before taking any medication, or if you have or suspect you might have a health problem. You should not stop taking any medication without first consulting your physician.
These statements have not been evaluated by the FDA. These products are not intended to diagnose, treat, cure, or prevent any disease.
References & Citations
All links retrieved on June 17th 2007.
1 Gynecol Oncol. 2007 Apr;105(1):23-30. Epub 2007 Jan 17: Genistein-induced apoptosis and autophagocytosis in ovarian cancer cells.
2 Phenoxodiol FAQ: http://marshalledwardsinc.com/index.cfm?section=03&subsec=0310
3 www.naturalproductsinsider.com/articles/9a1study.html
4 http://www.lef.org/magazine/mag99/june99-report2.html
5 http://www.uihealthcare.com/news/news/2004/05/17glucose.html
6 Gynecol Oncol. 2006 Jan;100(1):205-9. Epub 2005 Sep 19: Prolonged stabilization of platinum-resistant ovarian cancer in a single patient consuming a fermented soy therapy. (see attached PDF article for full research)
7 http://www.haelanresearchfoundation.com/HRF4.pdf
8 http://www.aacr.org/home/about-us/news.aspx?d=743 (based on UCLA research)
9 http://www.annalsnyas.org/cgi/content/abstract/1030/1/162
10 New York Academy of Sciences: http://www.annalsnyas.org/cgi/content/abstract/1030/1/162
11 Wikipedia: http://en.wikipedia.org/wiki/Autophagy
12 Wikipedia: http://en.wikipedia.org/wiki/Isoflavone
13 Medscape: http://www.medscape.com/viewarticle/409604_3
14 Zhang Y, Hendrich S, Murphy PA. Glucuronides are the main isoflavone metabolites in women. J Nutr 2003;133:399 – 404.
15 AACR Abstract: http://www.annieappleseedproject.org/gensoyingluc.html
16 DTIC: http://stinet.dtic.mil/oai/oai?&verb=getRecord&metadataPrefix=html&identifier=ADA409636
17 http://www.freepatentsonline.com/20020193319.html