Lab Study Shows Methadone Breaks Resistance in Untreatable Forms of Leukemia
August 1, 2008
PHILADELPHIA - Researchers in Germany have discovered that methadone, an agent used to break addiction to opioid drugs, has surprising killing power against leukemia cells, including treatment resistant forms of the cancer.
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."
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. Theirs is the first study to look at use of the agent in leukemia, specifically in lymphoblastic leukemia T-cell lines and human myeloid leukemia cell lines.
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.
Friesen said the research team is beginning to study methadone treatment in animal models of human leukemia, and she also says that other cancers might be suitable for treatment with the agent.
In this study, the single doses used to kill leukemia cells were greater than doses used to treat opioid addiction, but the researchers have since found that they can use a daily low dose of methadone to achieve the same effect. Friesen adds that while methadone can, itself, become addictive, that addiction is much easier to break compared to addiction to true opioids. "Addiction shouldn't be an unsolvable problem if methadone is ever used as an anti-cancer therapy," she said.
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The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes more than 28,000 basic, translational and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and 80 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication and its sixth major journal, Cancer Prevention Research, is dedicated exclusively to cancer prevention, from preclinical research to clinical trials. The AACR also publishes CR, a magazine for cancer survivors and their families, patient advocates, physicians and scientists. CR provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship and advocacy.