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Marine moss reveals clues to anticancer compound

PORTLAND, Ore. - An Oregon Health & Science University researcher believes the discovery of a gene cluster from a bacterium that protects a moss-like marine invertebrate from predators may be the first step toward engineering cancer-fighting drugs.

Margo Haygood, Ph.D., professor of environmental and biomolecular systems at OHSU's OGI School of Science & Engineering, has detailed her research team's discovery of the large gene cluster in a bacterium that protects the larvae of the bushy marine bryozoan Bugula neritina.

The bacterium, Endobugula sertula, acting as a symbiont to its bryozoan host, secretes a bioactive molecule that makes the poppy seed-sized larvae distasteful to predatory fish. But that molecule, known as a bryostatin, also confounds a variety of cancer cell lines.

"The larvae are covered with a skin of bryostatins," said Haygood, whose research was described recently in the Journal of Natural Products. "They need this kind of protection. We also discovered there are bryostatins on the root structures of the adults, perhaps to help them maintain their territory. But their main function is protecting the larvae."

And, it turns out, protecting people. Scientists have long known bryostatins, particularly a type of the compound called bryostatin 1, have anti-cancer properties, including activity against pancreatic and renal cancer, leukemia, non-Hodgkin's lymphoma and melanoma that involves flipping a switch that makes the cancer cells behave like normal cells. Bryostatin 1 is even in phase I and II clinical trials alone and in combination with other drugs.

But the problem has been getting the bryostatins in the large quantities needed for pharmaceutical development. Culturing the bacteria, for example, is challenging because the organism doesn't adapt well to conditions outside the narrow range provided by the host bryozoan. In addition, aquaculture of the bryozoan to produce the compounds is
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Contact: Jonathan Modie
modiej@ohsu.edu
503-494-8231
Oregon Health & Science University
8-Mar-2007


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