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Science Forum Index » Medicine - Cancer Forum » Lab study shows methadone breaks resistance in...
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| Steve... |
 Posted: Sun Aug 03, 2008 12:12 am |
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http://www.eurekalert.org/bysubject/medicine.php
Public release date: 1-Aug-2008
American Association for Cancer Research
Lab study shows methadone breaks resistance in untreatable forms of leukemia
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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