Sponge Poison Kills Cell Motors

A toxin that jams a common cellular motor has been discovered in a marine sponge. The compound, described in the current issue of Science, could perhaps be modified to keep cancer cells from dividing.

Cellular motors called kinesins drag cargo within cells--they tug recently separated chromosomes to opposite ends of a dividing cell, for example. Although scientists have found dozens of different kinesins, each with its own job, they know little about how the minimotors work. Lawrence Goldstein and his colleagues at the University of California, San Diego (UCSD), reasoned that if they could find a molecule that halts kinesin function, they could learn more about when and how they work--and possibly design drugs to disable specific kinesins.

The group decided to sort through what Goldstein calls the "weird-looking compounds" that John Faulkner and his colleagues at UCSD's Scripps Institution of Oceanography are purifying from marine animals. After testing dozens of candidates, the researchers found adociasulfate-2 (AS-2), a defense chemical used by a purple ropelike sponge that lives in the western Pacific Ocean. The researchers found that AS-2 binds strongly to the kinesin motor, preventing it from sticking to a cell's monorails--that is, traveling along microtubules. "The motor locks on and won't let go," Goldstein says. At high enough concentrations, AS-2 can completely seize up the motor.

"It's an excellent piece of work," says Jonathon Howard, a biophysicist at the University of Washington, Seattle. He notes that AS-2 could be the starting point for designing anticancer drugs to throttle the kinesin motor that allows cells to divide. These compounds might offer an alternative to drugs such as taxol, which attacks microtubules but has the side effect of damaging some nerve cells and decreasing a patient's white blood cell and platelet count.

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