Toxin Combo May Treat Leukemia

Arsenic, bryostatin may be potent therapy for blood cancers

TUESDAY, March 16, 2004 (HealthDayNews) -- A combination of two natural toxins -- arsenic and bryostatin -- may be a powerful new treatment for certain kinds of leukemia, claims a study in the March 16 issue of the Proceedings of the National Academy of Sciences.

Researchers at Johns Hopkins Kimmel Cancer Center found that arsenic, long used to treat certain leukemias, activates the same cellular self-destruct mechanism as bryostatin, a toxin that's found in coral-like aquatic organism called a bryozoan that attaches to piers, boat hulls, and rocky surfaces.

Arsenic is known to be effective against treatment-resistant acute promyelocytic leukemia (APL). It's a cancer of the blood and bone marrow characterized by unhealthy white blood cells. APL is a subtype of acute myeloid leukemia, the most common form of adult leukemia.

Until now, scientists didn't fully understand how arsenic actually kills cancer cells. The Johns Hopkins scientists used molecular studies to discover that arsenic activates NADPH oxidase, an oxygen-producing enzyme complex.

"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. Chi V. Dang, vice dean for research and professor of medicine, cell biology, pathology, and oncology, says in a prepared statement.

"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," Dang says.

But he and his colleagues found arsenic alone didn't pack quite enough punch; it left much of the NADPH dormant.

The Johns Hopkins scientists turned to bryostatin. Previous molecular studies found bryostatin also activates NADPH.

"So, we used bryostatin to wake up the rest of (the NADPH)," Dang says.

This combination requires further study in cells and animals before clinical trials can be conducted on people with APL.

More information

The American Cancer Society has more about leukemia.

SOURCE: Johns Hopkins Medical Institutions, news release, March 15, 2004
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