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Drugs from the deep blue

ry low concentrations. It appears to block cancer cells from dividing at a different, earlier step than that targeted by other clinically important anticancer drugs.

"It uses a different mechanism to any known drug, it's unlike anything else," Molinski said.

Chemists are now investigating phorboxazole and related compounds to see if they can be made more efficiently.

"It's excited a lot of chemists and cancer biologists," Molinski said.

Molinski's group has also gone fishing for drugs that modulate calcium channels within cells, in collaboration with Isaac Pessah, professor and director of the Center for Children's Environmental Health at the UC Davis School of Veterinary Medicine. The controlled release of calcium is a key step in many cellular processes.

"In any cell you can think of, calcium plays a role in shaping responses, activating or inhibiting enzymes, changing the shape of the cell, triggering cell division," Pessah said. Calcium is also a key signal in both fertilization and programmed cell death, he said. Pharmaceuticals that affect calcium channels range from drugs given to organ transplant patients to suppress the immune system, to treatments for high blood pressure and heart disease.

Pessah's research group works with calcium channel modulators and other biomolecules derived from plants and scorpion venom. But when Pessah and Molinski got to talking at a party some years ago, they quickly realized that they could apply the same methods to screen 124 sponges that Molinski's group had recently collected off the coast of Western Australia.

In one of the samples they came up with xestospongin C, the first of a class of drugs now widely used in research studies on calcium transport. Xestospongins block the ability of a signaling molecule called inositol 1,4,5 trisphosphate (IP3) to trigger the release of calcium within cells.

In most cases, scientists do not know why marine organisms make the
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Source:University of California - Davis


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