Thursday, February 05, 2009

Anti-cancer supplement interferes with cancer drug

Herbal supplements are increasingly popular as both prevenative and potentially curative alternative medicine. Often, they're taking alongside standard medication with the underlying assumption that there's no real downside: At best, they'll help; at worst they do nothing. We now know this isn't necessarily the case. For example, St. John's Wort, echinacea and even grapefruit are known to change the bioavailability of certain drugs by acting on cytochrome P450s.

One of the most popular supplements is green tea - consumed either as tea or in more concentrated supplement forms - whose most active polyphenol, EGCG, has been shown to have anti-cancer effects. That being the case, it's no surprise that many cancer patients complement their treatment by consuming green tea.

This may not be a good idea, depending on the chemo drugs being used.

A recent paper in the journal Blood (subscription required, press release here) demonstrates that green tea supplements can interfere with at least one particular chemotherapeutic.

The drug in question is bortezomib (aka Velcade), a proteasome inhibitor that induces ER stress leading to cell death and approved for treatment of multiple myeloma and mantle cell lymphoma. One of the pro-survival regulators in the ER stress response is GRP78. EGCG is known to inhibit GRP78 activity which may be the reason it can senstitize cells to other chemo agents. To the surprise of the researchers involved, the opposite was seen with bortezomib, and the drug's anti-tumor activity was almost completely negated. This was shown both in vitro and in vivo with different cancer models - multiple myeloma and glioblastoma. More importantly, the inactivation of the drug was found to occur with physiologically relevant concentrations of EGCG:
The study findings may have several important implications in the clinical setting. The EGCG blocked bortezomib’s antitumor effects at levels that are commonly achieved with the use of available concentrated green tea supplements (as low as 2.5 μM – which can be attained with two to three 250 mg capsules of green tea extract) suggesting the impact is very real for patients supplementing their therapy. The team also believes that as the EGCG inactivates bortezomib’s function in the tumor cell, it may also prevent some of the side effects that usually accompany the therapy. As a result, patients taking green tea products to supplement their therapy may experience improved well being and feel encouraged to increase their intake while unknowingly blunting or completely negating the efficacy of their bortezomib treatment.
EGCG was found to block bortezomib's proteasome inhibitory activity by directly interacting with the boronic acid group of the drug, forming a new adduct. Vitamin C has a similar, but much less potent, effect.

Of course, this is one very specific interaction and the authors note that it shouldn't minimize any previous beneficial effects reported for green tea. At the same time, it's an example of how complementary medicine doesn't get a free pass for being 'natural'.


Corey said...

Grapefruit acts on cytochrome P450s in the intestines, and can increase bioavailability of drugs.

Kamel said...

Yes, you are right. It's the other two that act in the liver. I've fixed that in the text.

It may also interfere with p-glycoprotein and screw up drug availability that way.