Gewone sierplant tegen kanker.*
Extracten
van de wortels van een gewone sierplant lijken veelbelovend te zijn in de
ondersteuning van therapieën tegen CML (chronische myeloïde leukemie). In dit
onderzoek werden de processen duidelijk waardoor CLM zich verder ontwikkelde en
dat het extract deze ontwikkeling kan stoppen zelfs in patiënten met Gleevec-resistant
cellen.
De plant is de coleus forskohlii, een soort siernetel en het wortelextract heet forskolin. Uit dit onderzoek blijkt dat forskolin een bepaald enzymproces opgang kan brengen dat kanker doet onderdrukken, de celgroei met 90% doet afnemen, de dood van kankercellen bevordert en gezonde cellen intact laat.
Backyard
Garden May Yield Leukemia Treatment
Scientists
here have identified a new pathway in the progression of chronic myelogenous leukemia
(CML). They also discovered that an extract from the root of a common ornamental
plant can suppress the process.
The
findings, appearing in the November issue of Cancer Cell, may yield new
treatment options for the estimated 4,600 people in the United States who are
expected to develop CML this year – especially those with advanced disease, or
those who become resistant to the drug Gleevec.
The
promising new extract is forskolin, which comes from the root of the plant
coleus forskohlii, a native of India that is used in the United States as an
ornamental plant.
Early
results on CML patient cells both in culture and in mice showed that forskolin
reduced the cancer cells' ability to grow by up to 90 percent.
“We
believe these are significant findings,” said Danilo Perrotti, a member of the
OSU Comprehensive Cancer Center 's Molecular Biology and Cancer
Genetics Program and an assistant professor in the department of molecular
virology, immunology and medical genetics. “We
have uncovered a key process that underlies progression in CML and identified an
agent that can block it. We also have shown that forskolin can reinstate normal
cell functioning, even in Gleevec-resistant cells that do not respond to any
treatment currently available.”
CML
arises when two chromosomes – 9 and 22 – mistakenly exchange genetic
material during cell division. The translocation creates a new, fused gene (called
BCR-ABL), that produces a cancer-causing enzyme called Bcr-Abl. Bcr-Abl
permanently “turns on” cell growth signals that are normally held in check
by molecules called phosphatases, and the result is the uncontrolled production
of white blood cells, the hallmark of CML.
Patients
with the earliest form of the disease – called the chronic phase – may not
even be aware they are sick. If the disease is discovered early, it almost
always responds to the drug Gleevec, which puts the brakes on Bcr-Abl activity.
The Food and Drug Administration (FDA) approved Gleevec as a treatment for CML
about five years ago and it was initially hailed as the first “wonder drug”
for cancer.
But
since then, a significant minority of patients who initially responded well to
Gleevec have acquired additional mutations and developed resistance to the drug.
In these patients, white blood cells continue to proliferate. If left unchecked,
it leads to the final, acute stage, called the blast crisis, where immature
white blood cells infiltrate the blood and the bone marrow.
Clinicians
are well-versed in the signs and symptoms of the
different stages of CML, but until now, they have had few clues about what
actually causes the disease to progress.
Perrotti
said his studies show that it may be due to the increased activity of Bcr-Abl
itself.
Through
extensive chemical and genetic tests conducted in
collaboration with an international group of researchers, Perrotti determined
that Bcr-Abl stimulates a protein called SET, which, in turn, inhibits the
phosphatase PP2A. PP2A is important because it acts like a tumor suppressor,
applying the brakes to growth signals stuck in the “on” position. When PP2A
isn't working properly, cancer cells are free to grow and spread.
While
PP2A suppression occurs in other forms of cancer, Perrotti said their tests
reveal that in CML, it only occurs in the blast crisis, not in the chronic phase
of the disease.
From
earlier studies, Perrotti recalled that forskolin could restore PP2A function.
Even though forskolin is currently used in Japan as a broncho- and vaso-dilator
and has been tested and found safe in clinical trials in Austria among patients
with asthma, it has not been approved by the FDA for use in the United States .
Perrotti
and his research team tested the effects of forskolin on normal, Gleevec -sensitive
and Gleevec-resistant CML cells, and discovered that the extract restored normal
PP2A function, reduced the cancer cells' ability to grow by up to 90 percent and
induced leukemic cell death and differentiation. It had no adverse effects upon
normal cells.
Interestingly,
when leukemic mice treated with forskolin stopped getting the treatment, some
died of leukemia and others showed evidence of Bcr-Abl activity. But starting
treatment again with forskolin – even weeks after initial treatment had
stopped – blocked Bcr-Abl activity and reinstated normal cell functioning.
Is
forskolin, then, a potential treatment for patients with CML who have already
advanced to the blast phase? It may well be, but Perrotti says additional
pre-clinical and pharmacologic studies must still be conducted to further assess
the therapeutic relevance of forskolin in patients with leukemia.
Several
agencies and organizations supported the research, including the National Cancer
Institute, The U.S. Army CML Research Program, the Elsa Pardee Foundation for
Cancer Research, the Lauri Strauss Leukemia Research Foundation, the Leukemia
Clinical Research Foundation and Fonds de la Recherche en Sante du Quebec.
Editor's Note: The original news release can be found here. (December 2005)
