Those smelly mothballs grandma has in her closet do more than just keep her sweaters free of holes. They cause cancer in mice and possibly humans, and now researchers may have figured out why. A study of the nematode worm Caenorhabditis elegans suggests that chemicals in mothballs shut down the natural process by which cells commit suicide, allowing cancer cells to divide and conquer.
The finding is serendipitous. When a neighboring lab became infested by mites, biochemist Ding Xue of the University of Colorado in Boulder tried to protect his C. elegans by putting mothballs in their containers. But the balls may have done more harm than good. Some of the worms' cells that were programmed to apoptose--or kill themselves--kept living indefinitely, a problem that has been linked to cancer in humans.
To figure out what was going on, Xue and colleagues isolated a chemical commonly used in mothballs called naphthalene. When worms were grown on top of an oil film containing the chemical, about a fifth of them had at least one cell survive that should have killed itself. And when worms with a defective apoptosis enzyme known as a caspase encountered naphthalene at levels similar to those seen with human mothball use, the animals had seven more cells survive in their pharynx than normal worms did. Unexposed mutant worms had on average only 1.5 extra cells, indicating that naphthalene exacerbates the problem.
The caspase itself appears to be napthalene's target. Incubating the worm caspase or a related human caspase directly with naphthalene nearly wiped out the enzyme's activity, the team reports online 14 May in Nature Chemical Biology. The lack of a working caspase would throw a wrench into the entire apoptotic pathway, Xue says, because it would prevent necessary downstream signals from firing and inducing cell death. He notes that many proteins in the cell death pathway are conserved between C. elegans and humans, so it's likely that naphthalene has a similar effect in people and could promote tumor growth with regular exposure.
"It's a good lead," says nematode biologist Carl Johnson of the Hereditary Disease Foundation in New York City. Though he believes the leap from worms to humans is too great to make at this stage, he says it's significant that even a human caspase was blocked by mothball compounds. "It shows that there is a comparable pharmacology."
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