Their laboratory study, published in the August 1 issue of Cancer Research, a journal of the American Association for Cancer Research, suggests that methadone holds promise as a new therapy for leukemia, especially in patients whose cancer no longer responds to chemotherapy and radiation.
"Methadone kills sensitive leukemia cells and also breaks treatment resistance, but without any toxic effects on non-leukemic blood cells," said the study's senior author, Claudia Friesen, Ph.D., of the Institute of Legal Medicine at the University Ulm.
"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," Claudia said.
Methadone, developed in Germany in the 1930s, is a low cost agent that acts on opioid receptors, and thus is used as an opioid substitute to treat addiction. Scientists have found that opioid receptors also exist on the surface of some cancer cells for reasons that are not understood. One research group tested the agent in human lung cancer cell lines and found that it can induce cell death.
In this study, Friesen and her colleagues tested methadone in leukemia cells in laboratory culture because this cancer also expresses the opioid receptor.
They found that methadone was as effective as standard chemotherapies and radiation treatments against non-resistant leukemia cells, and that non-leukemic peripheral blood lymphocytes survived after methadone treatment.
To their surprise, they found that methadone also effectively killed leukemia that was resistant to multiple chemotherapies and to radiation.
Probing the mechanism of methadone's action, the researchers found that it activates the mitochondrial pathway within leukemia cells, which activates enzymes called caspases that prompt a cell into apoptosis, also known as 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.