Smac-ing back at cancer cells( dded the Smac mimic to glioblastoma cul...)

"One particularly important finding is that the compound is effective at extremely low concentrations, already below those necessary for other commonly used anti-cancer drugs to work," said Wang. The low dosage needed to kill the cells suggests that as a therapy, the molecule may have fewer non-specific toxic side effects than many anti-cancer drugs.

IAP is also involved in another apoptotic process -- that triggered by a receptor protein called TNF alpha, which also triggers the inflammation process. The researchers found that Compound 3 also switched on apoptosis in cells treated with TNF alpha. Thus, said Wang, Compound 3 might also be used as an anti-inflammatory drug.

"Although this is still a hypothesis, it might be that, for example in rheumatoid arthritis, if we treated with something like Compound 3, it would cause TNF alpha to trigger apoptosis in the cells that cause joint and tissue damage. Thus, the secondary inflammation from these cells would be prevented."

However, he said, further studies in his laboratory will concentrate mainly on using Compound 3 as a prototype treatment for cancers. The researchers are currently testing the molecule's effects on an array of cultured cancer cells. They also plan to begin testing the compound in animal models of cancer, to explore its effectiveness, stability and distribution in vivo.

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Contact: Jennifer Michalowski
michalow@hhmi.org
301-215-8576
Howard Hughes Medical Institute
8-Sep-2004