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Cells re-energize to come back from the brink of death

rt-lived if CICD is activated. However, some cancerous cells not only dodge death from apoptosis by eliminating caspase activation, but they also foil CIDC. Our study sought to understand how a cancer cell without caspase activation bypasses CICD as well, Green said.

The St. Jude team discovered that a cell that lacks caspase activation and cannot undergo apoptosis increases the levels of an enzyme called GAPDH in order to counteract CICD. GAPDH appears to prevent CICD by supporting the functioning of the mitochondria and triggering the activity of certain genes that prevent or repair cell damage. The findings also suggest that the increase in GAPDH provides energy to increase autophagythe process by which a cell chews up debris and broken components, such as damaged mitochondria. After disposing of damaged mitochondria the cell can replace these vital components.

We found that in the absence of caspase activation, cells that avoided CICD took about a week or so to begin multiplying again, Green said. This might represent the time it takes for the cell to restore enough mitochondria to allow the cell to function normally.

The discovery that GAPDH appears to save cells from CICD suggests that blocking this enzyme would kill abnormal cells that lack caspase activation and cannot undergo apoptosis. That strategy would be the basis of novel anti-cancer drugs.

The St. Jude study was conducted in culture dishes in which normal cells were exposed to cancer drugs or other agents that triggered apoptosis. The researchers then blocked apoptosis in order to study CICD. The GAPDH response appears to represent a basic, reproducible event. But in order to verify that hypothesis, well need to study it in the body, especially as we try to develop ways to force cancer cells without caspase to undergo CICD, Green said. Our goal is to find better ways to treat these diseases.


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Contact: Summer Freeman
summer.freeman@stjude.org
901-495-3061
St. Jude Children's Research Hospital
1-Jun-2007


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