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'.

Cancer Research Blog Carnival

The bayblab is proud to host the first ever blog carnival on cancer research. The purpose of the exercise was two-fold: Find out who blogs about cancer research, and share ideas on this topic. Hopefully this will be the first step in creating a community of cancer research bloggers and readers. So please visit the links and share your comments!

Synthetic biology:
The first story comes from our very own bayman. Bayman is the original founder of the bayblab blog, part philosopher part mad scientist he's done some great work on oncolytic viruses and is dreaming up methods to engineer smart cells to deliver virus payloads. In this post he tells us how synthetic biology may carve the way to create bacteria that essentially function as organic computers capable of discriminating between cancer and normal tissue: "The gate integrates two environmental inputs to produce a phenotypic output. As an example, they show how their circuit can be used to program bacteria to invade mammalian cells when the concentrations of two different extracellular chemicals fall within a certain range."

Imaging:
Our next story comes from Ramūnas Janavičius a clinical genetics doctor from Vilnius University in Lithuania. He maintains a blog about cancer genetics and is particularly interested in a personalized approach to treatment. In this post he tells us how a recent study in Lancet has shown that MRI scans are vastly superior at detecting ductal carcinoma in situ compared to standard mammograms: "What is a connection between MRI, DCIS and cancer genetics, you may wonder? It is now well established, that BRCA1-positive breast tissue has different histopathological appearance and course - its usually G3, estrogen negative and expressing basal-like phenotype. Recently published studies from Canada, Italy, Germany (btw, by the same author), the Netherlands and UK (MARIBS study) all similarly showed, that MRI outperforms mammography in BRCA1 breast cancers and annual MRI is now included as addition to mammography for TP53, BRCA1 and BRCA2 mutation carriers screening programs, performed from 30 till 49 years in UK and other countries. Cost effectiveness of MRI is also proven." Check also his post about a novel biomarker for prostate cancer...

Diet:
Next we have Ruth from the Biotech Weblog. Ruth originally from the Philippines studied paddy soil microbiology at the international rice research institute. She is now a freelance writer based in Singapore. In her post she talks about how some green tea components may be protective against cancer: "epigallocatechin gallate (EGCG) equivalent to 8-16 cups of green tea, might help some people strengthen their metabolic defense against toxins capable of causing cancer by boosting the production of enzymes which belong to the glutathione S-transferase (GST) family."

Smoking:
Next we have Ben, who is a medical/PhD student in Chicago studying lung cancer and lately RNAi. He is mostly famous for having been mentioned on the bayblab podcast. In this post he tells us how Phillip Morris had troves of unpublished data about side effects of smoking. Also does a good job of explaining how second hand smoking is worse than toking, which had always been a mystery to me: "While the group that published this article had previously shown that secondhand smoke is fourfold more toxic than mainstream smoke (that is, the smoke to which a smoker is exposed), the primary findings of the present paper indicate that NNK formation increases rapidly in the local surroundings over a period of several hours after a cigarette is put out. That is, secondhand smoke clearly is harmful, and it becomes worse, and potentially more carcinogenic, even after that which is generating it is eliminated. This suggests that the dangers of smoking extend far beyond the localized duration of a single lit cigarette and the time it takes to smoke it—specifically, up to 11 hours’ worth of danger, according to Philip Morris themselves, over 20 years ago"

Clinical trials:
Next we have Joe, from the Joe Oncology blog. Joe is the leader of two cancer centers in the southeast United States. Joe shares with us the difficulties of running clinical trials, with all the agency red tape and patient recruitment nightmares: "Another problem we have is recruiting enough patients to go on trial. Patients like the idea of clinical trials but they don't like the idea of possibly receiving a placebo. I wouldn't either. Thus many opt for traditional treatment until there are no other options. Many by then don't have the will, the energy, or the qualifications to go on a clinical trial."

Pharmaceuticals:
Next we have Konstantinos Vougas, a molecular biologist from Greece who specializes in proteomics and maintains the life sciences blog. In his post he wonders what will happen with overpopulation if a cancer sure is found, and whether pharmaceutical companies are going to share it with the less fortunates: "If you were the CEO of a pharmaceutical industry giant and your R&D team came up to you one day and said “We have the perfect anti-cancer vaccine and we can get rid of cancer once and for all”, would you give this vaccine to the public? In other words would you give up on a $75 billion/year market in the US only?"

Diagnostic:
Finally we have Lim from Singapore who maintains the wacky Fresh Brainz blog. Lim is a frequent commenter on the bayblab and quite a joker. He tells us how early diagnosis can cut mortality rates: "Current work is focused on DNA-based therapeutics. Prof. Hartwell gave an example of how this is helpful: in esophageal cancer, which used to have a very poor prognosis. This is because by the time clinical symptoms appear, the patient has already entered the late stage of the cancer. Now, the outlook for patients has improved because of the availability of new screening techniques. Samples are taken from people who suffer from Barrett's esophagus and examined for DNA changes, allowing a much earlier diagnosis of cancer. "

Well that concludes our first ever blog carnival on cancer research, I hope you've enjoyed these links. I want to thank all the bloggers who submitted posts, and hope we can do this again sometime!