Emory Report
October 20, 2008
Volume 61, Number 8



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October 20
, 2008
Puzzle connecting cancer drug and sepsis solved

By Quinn Eastman

A well-known anticancer drug also binds a protein in the human body that triggers sepsis, Emory researchers have revealed.

In mice, the drug paclitaxel can bring on symptoms resembling sepsis, a life-threatening inflammation caused by systemic infection. Luckily for thousands of cancer patients, paclitaxel doesn’t act similarly in humans.
Solving this puzzle could help scientists better understand how paclitaxel works and develop new drugs to quench sepsis, says infectious disease specialist Shanta Zimmer.

Zimmer teamed up with Jim Snyder, Emory’s director of biostructural research and an expert on paclitaxel and its chemical relatives, to probe how the drug binds to a protein called MD-2. MD-2 helps white blood cells sense the presence of bacterial products called endotoxins.

The team’s results were published in the Oct. 10 issue of Journal of Biological Chemistry.

“We were able to demonstrate that paclitaxel doesn’t induce an inflammatory response through human MD-2, but binding does occur,” Zimmer says. “The difference seems to be in a particular loop area of MD-2, which changes shape when MD-2 binds.”

Paclitaxel was found in the bark of the Pacific yew tree by National Cancer Institute scientists in the 1960s. Its main effect — separate from its interactions with MD-2 — is to interfere with cell division by locking microtubules, the building blocks of the cell’s internal skeleton, into place.