July 7, 2012

Honeybees' "Caulk" Stops Tumor Cell Growth

The resinous substance bees make from plants and use to patch their hives stops tumor cell growth.

Scientists from the University of Chicago Medical Center have found that a compound from honeybee hives arrests the growth of prostate tumors in mice. And the techniques the researchers used are likely to give a lot more information on how and why many natural remedies do — or do not — work.

Propolis is the honeybees' own caulk, used to patch holes in their hives. It's a resinous mixture that the bees obtain from trees and plants. Propolis has been used for centuries as a natural remedy for many ills, ranging from sore throats to allergies to burns. It's also shown some anti-cancer activity. But it's gained very little acceptance in the medical community because there's almost no solid evidence on how it works or if it works at all.

When CAPE was fed to the mice daily, the tumors stopped growing. When CAPE was no longer fed to them, the tumors began to grow again at their original rate.

It hasn't helped that propolis is a mixture whose chemical composition varies from hive to hive, much as honey does.

The Chicago researchers worked with a single compound from propolis called caffeic acid phenethyl ester (CAPE). They found that even small amounts of CAPE slowed the growth of tumor cell lines, isolated cells from tumors grown in the laboratory. They then tested low doses of oral CAPE in mice that had human prostate tumor grafts. Oral CAPE slowed tumor growth by about 50%.

When CAPE was fed to the mice daily, the tumors stopped growing. When CAPE was no longer fed to them, the tumors began to grow again at their original rate. This suggests that CAPE works by stopping tumor cell growth, not by killing them.

The researchers were able to take a closer look at how CAPE was doing this by going back to the laboratory-cultured cells and seeing what changes occurred in the cells' proteins when CAPE was administered. To do so, they used a technique invented in 2010 called micro-western blotting, an improvement on a 40-year old technique. Traditional western blotting is a technique for separating and identifying proteins. Unfortunately, it's time consuming, expensive, requires large amounts of sample and can only look at a few proteins at once.

DNA researchers had a similar problem but solved it in the 1990s through micro-arrays, basically a miniaturization breakthrough, allowing many more samples to be run at a once and requiring smaller sample sizes. Protein researchers were able to adapt this technique for their own uses in 2010. It's now made it possible to possible to examine hundreds of proteins from a single a cell or organism at once, instead of just a few. It may eventually allow researchers to investigate the full spectrum of proteins in a cell.

Using micro-western blotting, the researchers were able to find that CAPE affected specific proteins in two pathways (p70S6 kinase and Akt) that allow a cell to sense the amount of nutrients available to it, lowering the activity of these proteins. When nutrients are low, cells stop dividing. CAPE appears to limit production of proteins that tell cells they have enough nutrients to begin dividing.

This suggests that CAPE may be a useful co-treatment alongside chemotherapies that kill tumor cells. It will take clinical tests to find out if this is true. But the techniques used by the researchers may have broader applications in increasing our understanding of herbal remedies.

Honey has shown a definite ability to cleanse infected wounds. Yet doctors are reluctant to use it because little is known about how it works. And researchers rarely even want to study herbal remedies such as green tea or ginseng, remedies whose effectiveness remains a topic of debate. It doesn't help that these are all mixtures containing many compounds that may each have a variety of actions, unlike penicillin, which is one single compound. Micro-western blotting may help researchers identify what specific compounds in these remedies are doing at the cellular and molecular levels, increasing (or decreasing) their acceptability to Western medicine.

As well as giving protein researchers a chance to catch up with their fellow DNA researchers.

An article on the study appears in Cancer Prevention Research.

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