Arsenic Study May Point to Leukemia Treatments

A study of arsenic and leukemia showed why the old-fashioned, slow-acting poison sometimes works against cancer and may point to new treatments for leukemia, scientists said on Monday.

A team at Johns Hopkins University in Baltimore found arsenic works in a similar way to bryostatin, a toxin made by coral-like sea animals that has been investigated as a possible cancer treatment. Put together, the two could offer a less toxic alternative to treating some forms of leukemia, the researchers said. Arsenic has been used for centuries in medicine. It is known to work against treatment-resistant acute promyelocytic leukemia (APL), a cancer of the blood and bone marrow that affects white blood cells. APL is a subtype of acute myeloid leukemia, the most common form of adult leukemia. Dr. Chi Dang and colleagues said they set out to find how arsenic works. Using laboratory samples, the Johns Hopkins team found that arsenic targets an oxygen-producing enzyme complex known as NADPH oxidase. “When normal white blood cells engulf invading bacteria, NADPH oxidase produces a big burst of bad oxygen species (charged molecules of oxygen) which they dump into bacteria to kill it and, in the process, kill themselves,” Dang said in a 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.” But arsenic cannot activate this mechanism fully enough to kill the cancer on its own, Dang said. “Even with arsenic treatment, much of the NADPH oxidase remains dormant in our system,” Dang said. His team knew that bryostatin also activated NADPH oxidase, “so, we used bryostatin to wake up the rest of it,” he said. The combination killed tumor cells with one-tenth the usual dose of either drug given alone, they found. That could mean a less toxic cancer treatment, said Dr. Wen-Chien Chou, who also worked on the study. “Arsenic is similar to other chemotherapeutic agents in terms of its potential toxicity, and there’s a trade-off in how much harm you do to normal cells versus cancer cells,” Chou said. “Yet, the synergistic effects of combining two drugs that activate the same pathway may allow us avoid toxicity using such low doses.” (Source: Reuters Health News: MedLine Plus: March 2004)