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How 'IAP antagonist' chemicals kill tumors
Date:11/15/2007

Chemical compounds specially designed to neutralize proteins that would otherwise allow tumor cells to cheat death have been recognized for some time by scientists as a promising new avenue for cancer therapy. Now, two studies in the November 16, 2007 issue of the journal Cell, a publication of Cell Press, provide insight into just how these antagonists of the anti-deathso-called Inhibitor-of-Apoptosis (IAP)proteins work to fight tumors.

The researchers reveal that the compounds hit specific IAP proteins known as cIAPs. That came as a surprise, they said, because the chemicals had originally been designed to target another of the anti-death proteins. The studies further show that the small molecule inhibitors not only block the death-defying proteins, but they also actively engage other players that lead to the death of tumor cells. Meanwhile, the chemicals seem to have little effect on healthy cells.

There has been an effort for several years to look for IAP antagonists, which seem to be very good in causing cell death in cancer, said Domagoj Vucic of Genentech, Inc. in South San Francisco, who led one of the two studies. It was thought they might be used in combination with other drugs. But now, we show that these chemicals are capable of inducing apoptosis all on their own.

It appears that when you remove cIAP1 in sensitive cancer cells, it opens the tap and everything just goes [toward cell death], added John Silke of La Trobe University in Australia, who led the other study. cIAP1 seems to be critical in deciding the life-or-death balance.

Apoptosis or programmed cell death is a cell suicide mechanism with a major role in development and homeostasis in all animals, Vucic explained. It is now accepted that apoptosis is also an extremely important defense against tumors, Silke added.

Scientists initially discovered the IAP proteins capable of blocking cell death in, of all things, a caterpillar virus, Silke said
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Contact: Cathleen Genova
cgenova@cell.com
617-397-2802
Cell Press
Source:Eurekalert

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