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Combination of toxin and poison may be novel treatment for leukemia

Johns Hopkins Kimmel Cancer Center scientists have discovered why arsenic has long been a successful way to treat certain leukemias, and in the process have shown that a combination of the poison and a second naturally occurring toxin may provide a potent new therapy for them.

The researchers discovered that arsenic, a naturally occurring element, actually activates the same cellular self-destruct mechanism as a compound called bryostatin, a toxin found in coral-like aquatic organisms. The findings are reported in the March 16 issue of Proceedings of the National Academy of Sciences.

Used for centuries for a variety of medicinal purposes, arsenic was first used as therapy for cancer in post-revolution China and is known to be effective against treatment-resistant acute promyelocytic leukemia (APL), a cancer of the blood and bone marrow characterized by unhealthy myeloid or white blood cells.

The method in which arsenic kills cancer cells, however, was not fully understood until Johns Hopkins scientists used molecular studies to track the poison's target to NADPH oxidase, an oxygen-producing enzyme complex.

In their experiments, the researchers used a low-dose combination of bryostatin and arsenic to kill APL cell lines in the laboratory.

"When normal white blood cells engulf invading bacteria, NADPH oxidase produces a big burst of bad oxygen species which they dump into bacteria to kill it and, in the process, kill themselves," says Chi V. Dang, M.D., Ph.D., vice dean for research and professor of medicine, cell biology, pathology and oncology. "We found that in APL, arsenic triggers activation of NADPH oxidase and uses this natural bacteria-killing mechanism against the leukemia cells -- in essence, a self-destruct switch."

But arsenic alone is not enough, say the researchers. "Even with arsenic treatment, much of the NADPH oxidase remains d
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Contact: Vanessa Wasta
wastava@jhmi.edu
410-955-1287
Johns Hopkins Medical Institutions
15-Mar-2004


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