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Birch Bark Compound May Be Potent Prostate Cancer Fighter (press release)

Tuesday, September 26, 2006 by: NewsTarget
Tags: health news, Natural News, nutrition

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A compound found in the bark of the white birch tree -- betulonic acid, a derivative of betulinol -- may finally have been rendered a water-soluble, bio-available drug, and is already showing the potential to be a possible agent against prostate cancer -- in cell culture and in an animal model.

Researchers at the Weill Medical College of Cornell University in New York City may have ended a decades-long quest to turn betulonic acid -- a stubbornly water-insoluble compound -- into a form that can be readily absorbed in a living body.

"Years of research appear to have paid off, and now animal tests on this potential anti-cancer agent can finally proceed. Already, in mouse studies, we've found that our water-soluble compound -- called Boc-lysinated-betulonic acid -- has achieved up to 92 percent inhibition of prostate tumor growth compared to controls," says lead researcher Dr. Brij Saxena, the Harold and Percy Uris Professor of Reproductive Biology and professor of endocrinology in obstetrics and gynecology at Weill Cornell Medical College.

His team published their results in the latest issue of Bioorganic & Medicinal Chemistry.

According to Dr. Saxena, scientists have been aware of the anti-cancer potential of the birch bark compound betulinol, and its derivative, betulonic acid, since the 1970s.

"In cell cultures, researchers at the U.S. National Cancer Institute demonstrated that our betulinol derivatives targeted and killed a wide range of cancer cells such as those from breast, lung and other malignancies," he says. "However, on its own, betulonic acid is what we call 'hydrophobic' -- it does not dissolve in water. This insolubility has meant that we've never been able to test the compound in a living model."

Turning an insoluble compound into something more soluble and bio-available can be a tough challenge, and Dr. Saxena says his team has been working on the problem since the mid-1990s.

"Finally, by attaching a long-side-chain amino acid called Boc-lysine to betulonic acid, we came up with a chemical structure that looked promising," he notes. "Next, we needed a good solvent, so we used a mixture of phosphate-buffered saline that included 20 percent ethanol (alcohol) and 4 percent human albumin."

The result was Boc-lysinated-betulonic acid, a fully water-soluble form of betulonic acid.

"Of course, we worried that once it became water-soluble, betulonic acid would lose its anti-cancer punch," Dr. Saxena says.

That wasn't the case.

While betulonic acid has proven effective in culture against a wide range of cancer, Dr. Saxena's team focused on prostate cancer because it is so widespread and because there are no drugs that can stop this malignancy once it metastasizes beyond the prostate.

In cell culture, Boc-lysinated-betulonic acid inhibited the growth of human prostate cancer cells by nearly 96 percent, the Weill Cornell team reports.

And, in the first-ever in vivo trial conducted with the compound, the new drug inhibited the growth of grafted human prostate cell tumors in mice by up to 92 percent -- with no apparent toxic effects.

"Right now we aren't clear just how Boc-lysinated-betulonic acid kills prostate cancer cells, but it seems to induce apoptosis -- programmed cell death," says a senior author of this study, Dr. Premila Rathnam, of Weill Cornell. "It may also compete with androgens -- male hormones -- for a place on the tumor cell. Tumor cells need androgens to thrive, so it's possible Boc-lysinated-betulonic acid may block that effect."

Whatever the mechanism, the creation of a bio-available form of betulonic acid marks a potential breakthrough, the researchers say.

"It's been a real hurdle, and we've been waiting for this opportunity for a while," Dr. Saxena says. "Now, we can proceed with the in vivo dose-response and toxicity studies that may lay the groundwork for clinical trials."

The research has also opened a potential avenue to synthesize more water-soluble derivatives of betulinol for other types of cancer.

This study was funded in part by Marc Pharmaceuticals.

Co-authors included Dr. Arkadiy Bomshteyn, Dr. Meirong Hao, Ms. Eileen Kisilis, Dr. Meena Katdare and Dr. Ozgur Oktem -- all of Weill Medical College of Cornell University; and Dr. Lei Zhu, of Memorial Sloan-Kettering Cancer Institute, New York City.

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