Antioxidants May Block Molecular Messengers Used By Cancers

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March 10, 1997

ANTIOXIDANTS MAY BLOCK MOLECULAR MESSENGERS USED BY CANCERS

Johns Hopkins scientists may have identified how oxidants can worsen cancerous
cell growth and how antioxidants can suppress it. Antioxidants have long been thought to
fight cancer; the current findings give insight into how the protection may occur and how it
may be harnessed for anti-cancer therapies.
Previous studies suggest that oxidants, or oxygen-containing molecules called free-radicals,
play an important role in causing cancer and that antioxidants, or free-radical
scavengers, help suppress cancer. The current study adds a twist: Cancerous cells
themselves may be causing an overproduction of free-radicals. Acting as messenger
molecules, the free-radicals send signals through protein pathways that promote further
uncontrolled cell growth. Results suggest that antioxidants and substances that interfere
with the signaling proteins may block this process.
Results of the study, supported by the National Institutes of Health, are published in
the March 14 issue of Science. "Control of signaling pathways involving oxidants may explain why some
antioxidants appear to prevent development of certain cancers," says Kaikobad Irani, M.D.,
lead author and a cardiology fellow at Hopkins.
The scientists studied connective tissue cells expressing H-RasV12, a cancer-causing gene,
and non-cancerous cells. The cancer cells produced large amounts of a superoxide, a key
free-radical molecule that is produced from oxygen. The Hopkins team found that the
free-radical overproduction was suppressed when the cells carrying
genes called Ras or Rac1 produced proteins that blocked the superoxide from signaling the
cells to become cancerous. Treatment of the cells with two types of protein inhibitors also
blocked the signals. More importantly, runaway cell division also was slowed by treatment
of the cancerous cells with an antioxidant, N-acetyl-L-cysteine.
Results suggest that in cancerous cells transformed by the Ras gene, the free-radicals
are produced by pathways involving proteins called flavoprotein and Rac1 and send signals that promote uncontrolled cell growth even in conditions when non-cancerous cells would
not grow. Protein inhibitors and antioxidants may block those signals that increase runaway
cell growth, says senior author Pascal J. Goldschmidt-Clermont, M.D., formerly of Hopkins
and currently director of the Heart and Lung Institute at Ohio State University.
"Our results should help researchers understand important biochemical pathways in
cancer and contribute to the future development of treatment strategies," Goldschmidt says.
Other Hopkins authors were Yong Xia, M.D., Jay L. Zweier, M.D., and Steven
Sollott, M.D. Investigators at the NIH, University of North Carolina at Chapel Hill and
University of Michigan Medical Center also participated in the study.

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