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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