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Study reveals new metabolic safeguards against tumor cells
Date:8/19/2009

s in laboratory cell culture. They also emphasize that the experiments were not designed to mimic the effect of dietary antioxidants in the body. The researchers used two specific antioxidant compoundswhich are chemically distinct from those found in food and supplementsonly in order to understand how oxidants contributed to the metabolic defects.

"We think that genes with antioxidant activity play a much bigger role than antioxidant compounds administered from outside the body," says Brugge. "What happens with dietary antioxidants is much more complicated and not what we were trying to study."

Beyond cell suicide

The researchers had previously reported that when cells were endowed with a cancer-causing gene that prevents them from committing suicide, they still died when cut off from their extracellular environment. This puzzled researchers, who have long thought that apoptosis was the only way the cells could die.

In the recent study, Schafer and colleagues took a closer look, measuring the levels of proteins and molecules associated with metabolic activity in the displaced, but apoptosis-resistant, cells. They found that the cells had become incapable of taking up glucose, their primary energy source. Under the microscope, the cells also displayed telltale signs of oxidative stress, a harmful accumulation of oxygen-derived molecules called reactive oxygen species (ROS). The end result was a halt in the production of ATP, the molecular lifeblood that transports energy in the cells. The unmoored cells were literally starving to death.

"The idea that a lack of extracellular matrix can prevent cells from accessing nutrients hasn't been shown conclusively before," says Schafer. "Loss of glucose transport, decreased ATP production, increased oxidative stressall those things turn out to be interrelated."

To figure out what was wrong, the researchers took a straightforward approachthey tried to fix it. Schafer
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Contact: David Cameron
david_cameron@hms.harvard.edu
617-432-0441
Harvard Medical School
Source:Eurekalert

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