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Structures of marine toxins provide insight into their effectiveness as cancer drugs

Vibrantly colored creatures from the depths of the South Pacific Ocean harbor toxins that potentially can act as powerful anti-cancer drugs, according to research findings from University of Wisconsin-Madison biochemists and their Italian colleagues.

The research team has defined the structure of the toxins and provided a basic understanding that can be used to synthesize pharmaceuticals, according to a study published this week in the Proceedings of the National Academy of Sciences (PNAS).

"We've determined how this class of toxins interacts with actin," an important protein responsible for cellular structure and movement, says Ivan Rayment, a professor of biochemistry in the College of Agricultural and Life Sciences who worked with John Allingham, a postdoctoral fellow, on the study. "We're adding to fundamental understanding which will be taken up by others to simplify chemical synthesis of what could potentially be powerful cancer treatments."

The toxins, which are produced naturally by organisms that exist symbiotically on deep-sea sponges, work by disrupting the activity of actin, an abundant protein that gives structure to eukaryotic cells.

"Actin forms long chains, or filaments, that are essential for cellular locomotion, division and growth," explains Allingham. "Because cancer cell masses grow faster than other cells in the body, actin provides an excellent target for drugs that could inhibit such rapid growth."

Adds Allingham: "These marine toxins can knock out the lynchpins in these long chains or cap their ends and kill cancer cells. Moreover, initial work shows that even a low dose of these toxins can bring a significant response."

Prior to the study published in PNAS, it was known that the marine toxins affect several forms of cancer - but not how they worked, says Rayment. The recent findings will enable the toxins to be synthesized in a lab instead of harvested from the depths of the ocean floor, mea
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Source:University of Wisconsin-Madison


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