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Cancer cell 'bodyguard' turned into killer
Date:11/25/2008

CORVALLIS, Ore. If you're a cancer cell, you want a protein called Bcl-2 on your side because it decides if you live or die. It's usually a trusted bodyguard, protecting cancer cells from programmed death and allowing them to grow and form tumors. But sometimes it turns into their assassin.

Scientists knew it happened, but they didn't know how to actually cause such a betrayal. Now they do. And it may lead to the development of new cancer-fighting drugs.

Researchers at Oregon State University and the Burnham Institute for Medical Research in La Jolla, Calif., have developed a peptide that converts the Bcl-2 protein from a cancer cell's friend to a foe.

"Now we can force this protein to backstab the cancer cell where it resides," said Siva Kolluri, an assistant professor of cancer biology in the environmental and molecular toxicology department at OSU. He's also the lead author of an article that reported the discovery in the Cancer Cell journal in October.

The key to the conversion is peptide NuBCP-9, a string of nine amino acids that bind to Bcl-2 and attack the mitochondria, the powerhouse of cells. Researchers derived it from Nur77, a nuclear receptor that can cause cells to die. To see if it worked outside the petri dish, researchers injected the peptide and its mirror-image molecule into cancer tumors in mice and found that the cancer cells died and the tumors shrank. To their surprise, they also found that a structurally mirrored-image stable peptide worked as well as the original peptide.

The findings could lead to the development of cancer-fighting drugs that target Bcl-2, Kolluri said. He explained that Bcl-2 is an attractive drug target because its levels are elevated in a majority of human cancers and it is responsible for cancer cells' resistance to many chemotherapeutic drugs and radiation.

Michael Melner, a scientific program director at the American Cancer Society in Atlanta, Ga., sa
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Contact: Siva Kolluri
siva.kolluri@oregonstate.edu
541-737-2940
Oregon State University
Source:Eurekalert

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