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"Methadone kills sensitive leukemia cells and also breaks treatment resistance, but without any toxic effects on non-leukemic blood cells," study senior author Claudia Friesen, of the Institute of Legal Medicine at the University Ulm in Germany, said in a news release issued by the American Association for Cancer Research. "We find this very exciting, because once conventional treatments have failed a patient, which occurs in old and also in young patients, they have no other options."
The findings were published in the Aug. 1 issue of Cancer Research.
Methadone blocks opioid receptors that exist on the surface of some cancer cells. In tests on leukemia cells in laboratory culture, methadone proved as effective as standard chemotherapies and radiation treatments against non-resistant leukemia cells. Methadone also effectively killed leukemia that was resistant to multiple chemotherapies and to radiation.
Unlike some treatments, though, non-leukemic peripheral blood lymphocytes still survived after methadone treatment.
Researchers found methadone activates the mitochondrial pathway within leukemia cells, which switches on enzymes called caspases. These prompt a cell into apoptosis, or programmed cell death. Chemotherapy drugs use the same approach, but methadone activated caspases in sensitive leukemia cells, and also reversed deficient activation of caspases in resistant leukemia cells.
While the doses of methadone used to kill leukemia cells in this study were greater than those used to treat opioid addiction, the researchers have since found a lower daily dose of methadone to achieve the same effect.
While methadone can become addictive, the habit is much easier to break than being hooked on true opioids, Friesen said.
"Addiction shouldn't be an unsolvable problem if methadone is ever used as an anti-cancer therapy," she said.
Studies using methadone in animal models of human leukemia are beginning, Friesen said, and others will look into whether the agent is also effective against other cancers. Another research group has already found methadone induces cell death in human lung cancer cell lines.
— Kevin McKeever
SOURCE: American Association for Cancer Research, news release, Aug. 1, 2008
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