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Common anti-inflammatory coaxes liver cancer cells to commit suicide
Date:5/16/2011

COLUMBUS, Ohio The anti-inflammatory drug celecoxib, known by the brand name Celebrex, triggers liver cancer cell death by reacting with a protein in a way that makes those cells commit suicide, according to a new study.

Researchers also found that the combination of celecoxib with each of two chemotherapy drugs killed more liver cancer cells in culture, making those combinations more effective than either drug on its own.

"Each chemotherapy drug alone will reduce the growth of cancer cells, but when each single drug is combined with Celebrex, a greater growth suppression effect was observed," said Jiayuh Lin, senior author of the study and an associate professor of pediatrics at Ohio State University. "For clinicians, this research suggests the possibility of a new therapeutic strategy."

Celecoxib has this effect by acting on STAT3, a gene inside liver cancer cells that, when activated, allows those cancer cells to resist the effects of chemotherapy drugs. The researchers determined that the celecoxib molecule binds to STAT3 on so-called "hot spots," effectively blocking its ability to function.

Powerful computing techniques were employed before the researchers ever considered celecoxib as a potential treatment for cancer. Celebrex is a nonsteroidal anti-inflammatory drug, or NSAID, and a Cox-2 inhibitor, meaning it helps control inflammation by inhibiting an enzyme known as cyclooxygenase-2. It is most commonly prescribed to treat the pain of arthritis.

Chenglong Li, an assistant professor of medicinal chemistry and pharmacognosy at Ohio State, has developed computer simulations to identify optimal drug fragment combinations that attach simultaneously to proteins in ways that block the proteins' functions. By searching a database of existing federally approved drugs, he found that celecoxib was structurally similar to a template molecule that he had determined would most effectively bind to STAT3 and inhibit it
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Contact: Jiayuh Lin
lin.674@osu.edu
614-722-5086
Ohio State University
Source:Eurekalert

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