Synthetic compound promotes death of lung-cancer cel...( DALLAS Nov. 12 2007 Human lung-can...)

DALLAS Nov. 12, 2007 Human lung-cancer tumors grown in mice have been shown to regress or disappear when treated with a synthetic compound that mimics the action of a naturally occurring death-promoting protein found in cells, researchers at UT Southwestern Medical Center report.

The findings, appearing in todays issue of Cancer Cell, suggest that the compound might one day be used in targeted therapies for lung and possibly other cancers, the researchers said.

We found that certain kinds of lung-cancer cells were sensitive to this compound, which sends a signal to cancer cells to self-destruct, said Dr. Xiaodong Wang, professor of biochemistry at UT Southwestern and senior author of the study.

In 2000, Dr. Wang announced the discovery of a cellular protein called Smac, which plays a key role in the normal self-destruction apparatus present in every cell. This process, called apoptosis, is activated when a cell needs to be terminated, such as when a cell is defective or becomes unnecessary during normal growth and development. In cancer cells, the self-destruct mechanism is faulty.

In 2004, Dr. Wang and his colleagues developed a compound that mimics the action of Smac. They found that in cell cultures, the compound killed cancer cells but left healthy cells unaffected. In those studies, however, the Smac mimic only killed cancer cells when it was introduced along with another molecule often involved in the cell-death machinery, called tumor necrosis factor-a, or TNFa.

In the current study, Dr. Wangs research group tested 50 human non-small-cell lung-cancer cell lines in culture and found that 22 percent of them were sensitive to the Smac mimic alone, without having to add TNFa. The researchers also found that the Smac mimic alone was effective against some types of breast cancer and melanoma cells in culture.

The apparent ability of a Smac mimetic, as a single agent, to induce cell death in n
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