Plant derivative attacks the roots of leukemia
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Date: 02/23/05
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Date: 23 Feb 2005 10:16:52 -0800
http://www.eurekalert.org/pub_releases/2005-02/uorm-pda022205.php
Public release date: 23-Feb-2005
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Contact: Leslie White
leslie_white@urmc.rochester.edu
585-273-1119
University of Rochester Medical Center
Plant derivative attacks the roots of leukemia
A daisy-like plant known as Feverfew or Bachelor's Button, found in
gardens across North America, is the source of an agent that kills
human leukemia stem cells like no other single therapy, scientists at
the University of Rochester Medical Center's James P. Wilmot Cancer
Center have discovered. Their investigation is reported in the online
edition of the journal, Blood.
It will take months before a useable, pharmaceutical compound can be
made from parthenolide, the main component in Feverfew. However, UR
stem cell expert Craig T. Jordan, Ph.D., and Monica L. Guzman, Ph.D.,
lead author on the Blood paper, say their group is collaborating with
University of Kentucky chemists, who have identified a water-soluble
molecule that has the same properties as parthenolide.
The National Cancer Institute has accepted this work into its rapid
access program, which aims to move experimental drugs from the
laboratory to human clinical trials as quickly as possible.
"This research is a very important step in setting the stage for future
development of a new therapy for leukemia," says Jordan. "We have proof
that we can kill leukemia stem cells with this type of agent, and that
is good news."
Parthenolide is the first single agent known to act on myeloid leukemia
at the stem-cell level, which is significant because current cancer
treatments do not strike deep enough to kill mutant cells where the
malignancy is born.
In other words, even the most progressive leukemia treatment, a
relatively new drug called Gleevec, is effective only to a degree. It
does not reach the stem cells, so "you're pulling the weed without
getting to the root," Jordan says.
Feverfew has been used for centuries as an herbal remedy to reduce
fevers and inflammation, to prevent migraine headaches, and to ease
symptoms from arthritis. (A person with leukemia, however, would not be
able to take enough of the herbal remedy to halt the disease.)
Investigating stem cells that give rise to cancer is an urgent new
initiative, as is identifying stem-cell treatments that might end the
disease process. Jordan and Guzman are among only a handful of stem
cell biologists nationwide who are specifically studying cancer stem
cells. In recent years, scientists have identified cancer stems cells
in blood cancers and in brain and breast tumors - although the idea
that cancer stems cells exist has been around for at least 40 years.
In the current study, the UR group began investigating Feverfew after
other scientists showed that it prevented some skin cancers in animal
models. Intrigued by the plant's anti-tumor activities, the UR team
analyzed how a concentrated form of parthenolide would act on the most
primitive types of acute myelogenous leukemia cells, chronic
myelogenous leukemia cells and normal cells.
In laboratory experiments, they also compared how human leukemia stem
cells reacted to parthenolide, versus a common chemotherapy drug called
cytarabine. The result: parthenolide selectively killed the leukemia
cells while sparing the normal cells better than cytarabine.
Scientists believe parthenolide might also make cancer more sensitive
to other anti-tumor agents. And, the UR group was able to demonstrate
the molecular pathways that allow parthenolide to cause apoptosis, or
cancer cell death, increasing the chances of developing a new therapy.
Jordan is director of the Translational Research for Hematologic
Malignancies program at the Wilmot Cancer Center and associate
professor of Medicine and Biomedical Genetics. Guzman is senior
instructor of hematology/oncology.
Other co-investigators include: Randall Rossi, associate scientist;
Lilliana Karnischky, laboratory technician; Xiaojie Li, technical
associate; Derick Peterson, Ph.D., assistant professor of
biostatistics, and Dianna Howard, M.D., at the University of Kentucky
Medical Center.
###
Their research is sponsored by grants from the Leukemia and Lymphoma
Society, American Cancer Society and National Cancer Institute.
--------------------------------------------------------------------------------
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