Hah, you didn’t think I had set the Polyhooligans aside just yet, did you?  😉  Well, as we know from my previous post, EZH2 is hyperactive (=overexpressed) in many types of cancer, including breast and prostate cancers and, of course!, myeloma. I have therefore been looking for PubMed studies on non-toxic substances that can perhaps help us restrain the antics of this particularly mischievous Polycomb repressor gene.

A September 2009 study (see: http://tinyurl.com/382xp66) confirms that the Aberrant expression of EZH2 has been associated with metastasis and poor prognosis in cancer patients. It then adds that, in spite of EZH2’s involvement in oncogenesis and therapy failure, not much is known about chemotherapeutics and chemopreventive agents that can suppress its expression and activity. Here, we show that dietary omega-3 […] polyunsaturated fatty acids (PUFAs) can regulate the expression of EZH2 in breast cancer cells.

Oh wait, duuuh, I just quoted from the publicly-available abstract…my apologies! But I did so because it makes an important point: in spite of the evidence pointing to EZH2 as a prime target in cancer treatment, very little is known about its potential inhibitors…Well, we have seen that curcumin is one such inhibitor…and today’s study shows that dietary omega-3 PUFAs (=polyunsaturated fatty acids) are also able to block EZH2.

The full study (that I received from a very kind blog reader–thank you!) begins with a description of the Polycomb group proteins (PcGs) and the Polycomb repressive complexes (PRCs), which are formed when PcGs stick to one another…okay, skip skip skip…this stuff is giving me a headache…I need to forge ahead and select only the important bits…

Here is one: Chemopreventive agents such as dietary polyunsaturated fatty acids (PUFAs) are known to influence the development and progression of breast cancer and other cancers. Omega-3 PUFAs lower a woman’s risk of developing breast cancer, whereas omega-6 PUFAs are associated with a higher risk. However, the study informs us that even though the molecular targets of PUFAs are not very well understood, one of these targets happens to be EZH2…Well, that is cause for celebration, I’d say!

The researchers examined DHA and EPA, two of the best-known omega-3 PUFAs, as well as LA and AA, which are omega-6 PUFAs*. EZH2 became less active when breast cancer cells were treated with DHA and EPA, whereas it was not affected at all by AA and LA. The study describes a series of experiments, but the language used is very technical, so yes, I think I will go directly to the Discussion part…

Here we learn (…but are undoubtedly not surprised!) that omega-3 PUFAs have been the object of many cancer studies. Out of curiosity, I went to PubMed and found hundreds of studies, including this pancreatic cancer one: http://tinyurl.com/35syxy4. Apparently, omega-3s can mediate cancer development and progression through multiple mechanisms. For example, they have an impact on NF-kappaB. Good news for us, obviously.

Skipping on…Recent genetic studies suggest that PUFAs are involved in the regulation of a broad spectrum of genes involved in diverse biological functions such as nutrition, cell division, proliferation, apoptosis and metastasis. Omega-3s can inhibit angiogenesis (=another process that helps keep MM cells alive and healthy) and COX2 (yep, this one, too, is another big friend of myeloma cells). Well, the list goes on and on. Let’s leave it and get back to our point…

The point is that DHA and EPA, two omega-3 PUFAs,, can decrease the activity of (=down-regulate) EZH2, one of the blasted Polycomb repressor genes that is involved in the proliferation of myeloma cells.

In the researchers’ own words, our studies suggest that anti-oncogenic effect of omega-3 PUFAs, at least in part is mediated by the PcG targets of PUFAs such as EZH2. And, they add, to the best of our knowledge, this is the first study that links the regulation of expression of PcG proteins, in particular EZH2, to chemopreventive agents such as dietary fatty acids. Let’s hope that it is not the last!

Even though I have to admit that I didn’t understand a good part of this study (e.g., the bits about EZH2 posttranslational regulation and EZH2 ubiquitination and subsequent degradation by proteosome-dependent pathways…Aaagh!!!), this much is crystal clear: we should, indeed we MUST include omega-3 PUFAs in our diet. I take 2 grams of molecularly-distilled fish oil every day and, after reading this study, have found another excellent reason for sticking to my protocol…

*More information on the difference between omega-3 and omega-6 PUFAs: http://tinyurl.com/5e33wd and http://tinyurl.com/3ywwf8f (there is a ton of information out there on omega-3s and omega-6s…a quick search is all you need to do…).