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Promise and Progress - Arsenic Part of Novel Treatment for Leukemia

Faces of Childhood Cancer

Arsenic Part of Novel Treatment for Leukemia

Date: June 1, 2004

Proceedings of the National Academy of Sciences, March 16, 2004

Chi V. Dang, M.D., Ph.D., has uncovered the reason arsenic has long been a successful treatment for certain types of leukemia and combined it with a second toxin to develop a new, more potent therapy. Dang and colleagues discovered that arsenic activates the same self-destruct mechanism in acute promyelocytic leukemia (APL) cells as a toxin called bryostatin found in coral-like marine organisms.

The research team tracked arsenic’s cancer-killing ability to an oxygen-producing enzyme complex called NADPH oxidase. “When normal white blood cells engulf invading bacteria, NADPH oxidase produces a big burst of bad oxygen species which they dump onto bacterium to kill it and, in the process, kill themselves,” explains Dang. He, Dr. Wen-Chien Chou and team found that in APL, arsenic triggers activation of NADPH oxidase and turns on the same self-destruction switch. But arsenic needs some help, according to Dang, and that’s where bryostatin comes in. “Even with arsenic treatment, much of the NADPH oxidase remains dormant in our system,” he says. However, bryostatin also activates the enzyme, and working in synergy the two toxins cause a big enough release of NADPH oxidase to kill off leukemia cells.

This research was funded by the National Cancer Institute.