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Combined Arsenic & Bryostatin Promising for Leukemia

Center scientists have discovered why arsenic has been a successful way to treat certain leukemias, and in the process have shown that a combination of arsenic and bryostatin may provide a potent new therapy. As detailed in a study in the March 16 issue of Proceedings of the National Academy of Sciences, the team found that arsenic activates the same cellular selfdestruct mechanism as bryostatin, a toxin found in coral-like aquatic organisms. The method by which arsenic kills cancer cells, however, was not fully understood until the researchers, led by Chi V. Dang, MD, PhD, Vice Dean for Research and Professor of Medicine, Cell Biology, Pathology, and Oncology, used molecular studies to track arsenic’s target to NADPH oxidase, an oxygen-producing enzyme complex. He and his colleagues used a lowdose combination of bryostatin and arsenic to kill acute promyelocytic leukemia (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,” Dr. Dang said in a news release. “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.” APL is a subtype of AML. But arsenic alone is not enough. “Even with arsenic treatment, much of the NADPH oxidase remains dormant in our system,” Dr. Dang said. However, previous molecular studies showed that NADPH oxidase also is activated by bryostatin, currently under clinical investigation for a wide variety of cancers.