March 19 2009 post. 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!