EGCG and bortezomib (Velcade): the full study

A blogging friend reminded me about the EGCG-Velcade study published on February 3rd 2009 in “Blood,” and that I posted about here on February 4th. Sherlock (grazieee!) retrieved the full study for me…but then I put it on my desktop and promptly, uhm…forgot about it. That happens. Oh well.

 

At any rate, this morning I read through it to see if there was anything I could add to what we know from the abstract (http://tinyurl.com/c9ppr2). There is.

 

Read this (BZM, by the way, is the acronym for bortezomib, marketed as Velcade): when BZM and EGCG were added together, the cell killing by BZM was completely prevented and cell survival remained at 100% […]. Yikes! This occurred even at low EGCG concentrations. Scary.

 

Another interesting discovery. This study’s findings contrast with previous reports about the cytotoxic (=toxic to cells) effect of EGCG on myeloma cells. The researchers only noted weak cytotoxic effects starting at 20 microM, which become somewhat more pronounced when drug exposure times are increased from 48 to 72 hours. Interestingly, even under conditions where EGCG is slightly toxic, it is still able to potently antagonize the cytotoxic effects of BZM. For example, in U266 cells, 20 microM EGCG alone reduces viability by 20% after 48 hours, and 10 nM BZM reduces viability by >95%—yet, when the two drugs are combined, viability is still only reduced by 20%. By the way, U266 is a myeloma cell line frequently used in these studies. Well, I must say, this bit of news is not encouraging AT ALL…Well, let’s go on.

 

The inhibiting effect of EGCG against bortezomib was observed also in vivo (nude mice with myeloma tumours, poor dears). I don’t need to go into any details, suffice it to say that the in vitro results were confirmed in vivo, too.

 

The researchers tested the antioxidant activity of EGCG to see if that could be the cause of its bortezomib inhibition, but no, that wasn’t it. They did confirm that EGCG is a powerful antioxidant, though, which is good news for green tea drinkers not on Velcade.

 

EGCG’s inhibiting activity is instead apparently due to the presence of boronic acid in BZM: The severe antagonistic effect of EGCG appeared to require the presence of the boronic acid moiety in BZM. Proteasome inhibitors that did not contain any boronic acid were not affected by EGCG. So EGCG has a problem with boronic acid, not proteasome inhibition per se.

 

Ah, in the Discussion part I read something that I didn’t know: Interestingly, it has been reported earlier that vitamin C, a 1,2-diol containing compound as well, is able to antagonize cell killing by BZM. Apparently, vitamin C reacts with the boronic acid contained in bortezomib and, like EGCG, inhibited its cancer killing effect. Not good. Another word of caution: if you are taking Velcade right now, please see also my report on dietary flavonoids and Velcade (scroll down my Pages on the right).

 

Well, this study certainly supports the importance of giving your cancer specialist a list of all the supplements that you would like to take. Especially if you are following a conventional course of treatment, and even more especially (!) if said treatment includes Velcade.

 

The study concludes: In humans, EGCG concentrations of 5–8 microM can easily be achieved after the ingestion of capsules containing GTE (polyphenon E). We therefore have no doubt that our discovery is highly relevant for clinical considerations and would strongly urge patients undergoing BZM therapy to abstain from consuming green tea products, in particular those widely available, highly concentrated GTEs that are sold in liquid or capsule form.

 

In conclusion, if you are currently taking Velcade, do not drink any green tea or take EGCG or vitamin C. You might feel better, but the anticancer effect of Velcade, unbeknownst to you, is probably being severely blunted, if not entirely obliterated. Not good!

 

By the way, I was so focused on the curcumin cell membrane ion channel studies that I completely missed celebrating my two-year blogiversary (=blog anniversary…I just coined a new word…or did I?) on March 17! Has it already been two years? Yep. Amazing how time flies…

8 Comments

  1. Happy 2nd blogiversary Margaret! I don’t think I’ve ever told you this before but now would be a good time. I first discovered your blog while I was at work. It was like a mirage! I couldn’t believe I had stumbled across such a wonderful, informative, easy to understand (?) conversation about a disease I knew NOTHING about and no one to ask except my oncologist who knew very little about it either! I could hardly wait to get home to look up “Margaret’s Corner” and read!

    Later that night I tried looking up your blog but I couldn’t find it! I was afraid it had been a dream. It took a while but I finally found it again! I was so thankful!

    I think I can safely say that the information I’ve found in your blog written by you and your readers has helped me continue to smolder for over 2 years now. You’re a God send to many of us! I thank you sincerely. Donna

  2. Margaret
    let me also say how helpful your site has for me.I am a viet nam
    veteran exposed to agent orange,diagnosed smm aug 2008,confused
    with little help from the VA medical center.Your site has help me
    understand and make choices that is beneficial to my health.
    I read your site first thing every morning to see “whats new”,plus
    reading and rereading about curcumin
    thanks
    JoJo

  3. Margaret,
    Miss a day (of margaret’s Blog) and you miss a lot. Always something new to chew on.
    Thanks
    Julie from Iowa

  4. Happy anniversary, Margaret! What a complete godsend this blog is to those of us in this unfortunate fraternity. I regularly quote you in conversation with both doctors and friends. You would be amazed at how little some of these specialists know about the research you have uncovered – thanks for informing us all!

    Egads, maybe I should give the Velcade a go again, this time w/o my usual tea and oj imbibing. Who knew?

  5. Happy Anniversary!
    I still like my conclusion better (grin).

    Ahem… “If you are taking Vitamin C, EGCG, or any form of Green Tea – DO NOT TAKE VELCADE – you might feel worse plus it won’t benefit you in the least!”

    Anyhow – you were more diplomatic (grin).

  6. My wife achieved a complete hematological response (AL amyloid) on Velcade. Last Velcade treatment was more than 3 months ago. Is EGCG now safe? This may sound as a silly question, but it is not for me. Thanks!

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