Recent research has indicated that in the process of generating
energy, leukemic cells use a cellular pathway known as fatty acid
oxidation, rather than pyruvate oxidation, as had been previously
thought. A team of researchers, at the University of Texas M.D.
Anderson Cancer Center, Houston, and the University of Texas Houston
Medical School, has now used this knowledge to develop a way to
sensitize human leukemic cells to molecules that induce cell death by
a process known as apoptosis. They hope that it might be possible to
translate this approach to the clinic as a therapeutic strategy to
treat leukemias.
The team, led by Michael Andreeff and Heinrich Taegtmeyer, found that
inhibition of fatty acid oxidation with either etomoxir, a drug that
was tested in clinical trials for the treatment of heart disease but
never made it to market due to unacceptable toxicities, or ranolazine,
a drug approved for the treatment of chronic angina, inhibited human
leukemic cell proliferation in vitro. More importantly, etoxomir
treatment sensitized human leukemic cells to the death-inducing
compound ABT-737 both in vitro and in vivo, in a xenotransplant mouse
model of leukemia. The authors therefore conclude that fatty acid
oxidation is essential for human leukemic cell survival and suggest
that inhibitors of fatty acid oxidation might provide a new approach
to treating leukemias.
TITLE: Pharmacologic inhibition of fatty acid oxidation sensitizes
human leukemia cells to apoptosis induction
AUTHOR: Michael Andreeff, University of Texas M.D. Anderson Cancer
Center, Houston, Texas, USA.
Journal of Clinical Investigation, December 21, 2009
Source: Karen Honey
Journal of Clinical Investigation
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