15-Oct-2005
Curcumin halts spread of breast
cancer in mice
Early study shows spice stunts deadly spread
to lungs
HOUSTON - Curcumin, the main ingredient of turmeric
and the compound that gives curry its mustard-yellow
color, inhibits metastasis to the lungs of mice
with breast cancer, report researchers at The
University of Texas M. D. Anderson Cancer Center.
The
study, to be published in the Oct. 15 issue
of the journal Clinical Cancer Research, reports
that the spice appears to shut down a protein
active in the spread of breast cancer to a major
target for metastasis.
Though
the study results are early, researchers found
that the nontoxic natural substance not only
repelled progression of the disease to the lungs,
but also appeared to reverse the effects of
paclitaxel (TaxolTM), a commonly
prescribed chemotherapy for breast cancer that
may trigger spread of the disease with use over
a long period of time.
Because
Taxol is so toxic, it activates a protein that
produces an inflammatory response that induces
metastasis. Curcumin suppresses this response,
making it impossible for the cancer to spread.
In fact, researchers found that adding curcumin
to Taxol actually enhances its effect. Curcumin
breaks down the dose, making the therapy less
toxic and just as powerful while delivering
the same level of efficacy.
"We
are excited about the results of the study and
the possible implications for taking the findings
into the clinic in the next several years,"
says Bharat Aggarwal, Ph.D., professor of cancer
medicine in M. D. Anderson's Department of Experimental
Therapeutics. "At this time, advanced breast
cancer is a difficult foe to fight with few
proven treatments available after surgery, chemotherapy
and radiation therapy."
Taxol
is currently used as the front-line chemotherapeutic
agent in breast cancers, but because the drug
frequently induces drug resistance after prolonged
use, it is not effective in treating metastatic
breast cancer, says Aggarwal.
Researchers
studied 60 mice with breast cancer, which were
randomly assigned to one of four groups: control
group, Taxol only, curcumin only and the combination
of Taxol and curcumin. After the tumors grew
to 10 mm (about the size of a pea), they were
surgically removed, and the mice were fed a
powdered curcumin diet.
Macroscopic
lung metastasis, or metastasis that is visible
to the naked eye, was seen in 96 percent of
the mice in the control group. Treatment using
Taxol alone only "modestly reduced" the incidence
of metastases, while the group using curcumin
alone and curcumin plus Taxol "significantly
reduced" both the incidence and numbers of visible
lung metastases.
Microscopic
metastasis, or metastasis that is visible only
when using a microscope, was found in the lungs
of 28 percent of mice treated with the combination
of curcumin and Taxol, and there was no macroscopic
disease present. The micrometastases present
consisted of only a few cells, suggesting that
the combination inhibited the growth of breast
cancer tumor cells that were in the lung before
the tumors were removed.
In
a previous study published in the Aug. 15 issue
of the journal Cancer, M. D. Anderson researchers
found that when the nuclear factor-kappa B (NF-kB)
(a powerful protein known to promote the inflammatory
response necessary to cause breast cancer to
spread) is shut down, cancer strains are unable
to grow and cells are pushed to commit suicide.
The
mechanism
in this curcumin study works the same way. Taxol
activated the NF-kB in breast cancer cells,
while curcumin stopped this activation by blocking
the protein known as "IKK" that switched on
the NF-kB, demonstrating how curcumin and Taxol
work against one another. Taxol produced the
inflammatory response, triggering metastasis,
and curcumin suppressed it, causing cell death.
Extracted
from the roots of the curcuma longa plant, curcumin
is a member of the ginger family. While it is
not used in conventional medicine, it is widely
prescribed in Indian medicine as a potent remedy
for liver disorders, rheumatism, diabetic wounds,
runny nose, cough and sinusitis. Traditional
Chinese medicine uses curcumin as a treatment
for diseases associated with abdominal pain,
and it is used in ancient Hindu medicine as
a treatment for sprains and swelling.
According
to the American Cancer Society, the chance of
a woman having invasive breast cancer sometime
during her life is one in eight. About 211,240
women in the United States will be diagnosed
with invasive breast cancer in 2005, and approximately
40,410 women will die from the disease this
year.
* * *
The study was funded by the United States Department
of Defense. Co-authors include Shishir Shishodia,
Ph.D.; Yasunari Takada, Ph.D.; Sanjeev Banerjee,
Ph.D.; Robert A. Newman, Ph.D.; Carlos Bueso-Ramos,
M.D., Ph.D.; and Janet E. Price, Ph.D.
