Do you remember all the hoopla caused by a June 2009 study on green tea and bortezomib? If not, please click here: http://margaret.healthblogs.org/life-with-myeloma/discovery-of-curcumin/curcumin-and-bortezomib/egcg-and-bortezomib That study came as very bad news for devoted green-tea-drinking patients on Velcade, even though, as Dr. Durie pointed out during a patient seminar that I attended last fall, those patients can still have their cuppa…just not on their Velcade days…

Now for today’s topic. Not too long ago, a blog reader (thanks!) reminded me of a November 2009 study that I had read in December but hadn’t posted about… Sherlock, grazie!, sent me the full study, whose main result is spelled out in the abstract (http://tinyurl.com/ydyaqca): EGCG is synergistic with bortezomib (=Velcade) against the KM3 multiple myeloma cell line. SYNERGISTIC??? That means that EGCG and Velcade are more efficient myeloma cell assassins when used together…

Wait a sec…in June we were told that EGCG antagonizes bortezomib (see: http://tinyurl.com/yfe24cl, full text also available for free)…this group of researchers found that not only was EGCG not toxic or (at higher concentrations) only mildly toxic to myeloma cells, but also it prevented bortezomib from doing its job. In other words, based on the June study, EGCG actually protected the myeloma cells…from bortezomib.  

When I first read and posted about the June study, I don’t remember being bothered by the occasionally arrogant language used by the authors…especially in this excerpt about EGCG: this “miracle herb” extract is also consumed by many cancer patients who follow popular trends and self-medicate with complementary and alternative medicine (CAM) in hopes to support their conventional therapy or to lessen the burden of side effects—sometimes without the knowledge of their health care provider. “Popular trrrends”??? I say, I am feeling quite offended right now…how did I miss that condescending tone when I first read the study last year? Well, I suppose I was more focused on the importance of the issue at hand, i.e., warning Velcade-users against taking EGCG or even drinking green tea…

I also (!) didn’t question the finding that EGCG, when used alone, wasn’t able to kill even one miserable little myeloma cell, even at concentrations that are much greater than the typical concentrations achieved in humans. This is contrary, e.g., to the results of an authoritative 2006 study (see: http://tinyurl.com/yzsdu38)… Makes me wonder…

One more thing. I would like to point out that, incredibly, the online media paid no attention whatsoever to the November pro-EGCG study, whereas the complete opposite is true of the June anti-EGCG study…in fact, if you do a quick online search, you will still find warnings, even recent ones, about drinking green tea with bortezomib…even if you type the words “EGCG” “bortezomib” and “synergy.”

What you will not find (at least I did not) is the slightest mention of the November 2009 study, the one with the synergy results. That story just wasn’t picked up, for…some reason (I can only guess…). Well, today I decided to fill the gap…not because I think that the November study is a better one, that is not for me to judge!, but because I don’t think it fair that this study be so blatantly ignored…

Okay, for reasons of simplicity, from now Study A will be the June anti-EGCG with bortezomib study, and Study B will be the November pro-EGCG with bortezomib study.

Just a quick glance at the two studies showed that there were differences in caspase activation…In Study A, EGCG blocked the activation of caspase-7, which essentially stopped bortezomib from exterminating the myeloma cells. In Study B, instead, EGCG activated different caspases, specifically caspase-3, -8 and -9, leading to the death of the myeloma cells. Some day I should really look into this caspase business…until then I will not be able to figure out how, why or if this might be significant (I’d be glad for some help, here!)…

For lack of time, sorry, I am going to jump to the Discussion part of Study B. As I had hoped, this is where the authors compare their own results to the ones of Study A (identified as “they” in the following excerpts):

-They use a relative [sic] lower concentrations of EGCG (10 mM) and bortezomib (10 nM), whereas we used a relative [sic] high concentration of EGCG (25, 50, and 100 mM) and bortezomib (20 nM). So let’s see…Study A used a lower dose of EGCG and bortezomib, Study B a higher one. Okay, that is certainly a difference.

-We focused on the mechanism of EGCG inhibiting myeloma cell growth and inducing cell apoptosis potentiated by bortezomib, whereas they focused on the effect of EGCG on bortezomib in myeloma cells. So, we found that EGCG inhibits myeloma cell growth and induces cell apoptosis potentiated by bortezomib. This part wasn’t clearly worded, in my opinion (but it is true that I just got over a cold…is my mind still fogged by a bit of congestion?). In fact, I don’t see any difference at all…Mental note: I need to find the time to compare how the experiments were carried out in both studies.

-This may be because of different drug concentrations or different cell lines. Study A and B (and even the above-mentioned 2006 study, by the way) tested EGCG and bortezomib on different myeloma cell lines. And different doses were used in both studies. Is that enough to explain their differing results? Possibly.

I found myself wondering about the different myeloma cell lines used in different studies. Interesting topic. I had no idea that there were so many myeloma cell lines. I began doing some research but had to give up. Too complicated and time-consuming…

Well, I admit, I am still baffled. I suppose that I would still be cautious about taking green tea or EGCG with Velcade. I would follow Dr. Durie’s suggestion. Best to be cautious. Still, Study B gives us some (green) tea for thought and shows how much we still have to learn…

P.S. Here is a list of things that Velcade patients should avoid taking: http://tinyurl.com/yk2tclg