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Methadone Inhibits Hard-to-Kill Leukemia Cells

Drug even induced apoptosis in cells resistant to doxorubicin, other common anti-cancer drugs

WEDNESDAY, Aug. 6 (HealthDay News) -- In addition to its use in treating opioid dependence, methadone kills leukemia cells, including types resistant to doxorubicin and other common anti-cancer drugs, researchers report in the Aug. 1 issue of Cancer Research.

Claudia Friesen, Ph.D., of the University of Ulm in Ulm, Germany, and colleagues conducted experiments using the human myeloid leukemia cell line HL-60 and the human lymphoblastic leukemia T-cell line CEM. After treating cells with different concentrations of methadone, the researchers found induction of apoptosis and inhibition of growth in the cells 24 and 48 hours later. However, incubating non-leukemic peripheral blood lymphocytes in methadone at concentrations similar to those used for treating leukemia cells didn't kill them.

Methadone also induced apoptosis in doxorubicin-resistant CEM cells, as well as CEM cells resistant to etoposide, cisplatin, methotrexate, cytarabine and vincristine, the investigators found. However, incubating cells with a caspase inhibitor beforehand almost totally inhibited methadone-induced apoptosis, which indicates that caspases play a crucial role in this beneficial effect. The researchers' work also suggests that the apoptosis is due to activation of the intrinsic mitochondrial pathway in leukemia cells.

"By providing the molecular basis of methadone-induced cell death in sensitive as well as in chemoresistant and apoptosis-resistant leukemia cells and by finding comparable activation of apoptosis pathways of commonly used anti-cancer drugs but with more potent effects in cell killing, especially in chemoresistant and apoptosis-resistant leukemia cells, this study provides the foundation for new strategies establishing methadone as an additional therapeutic anti-cancer drug in leukemia therapy," the authors conclude.

Abstract
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