Grape Seed Extract Causes Leukemia Cells to Commit
Suicide in Laboratory Test
Possible implications for prevention or treatment of
hematological malignancies, other cancers
Dec.
31, 2008 - An extract from grape seeds forces laboratory leukemia cells
to commit cell suicide, according to researchers from the University of
Kentucky. They found that within 24 hours, 76 percent of leukemia cells
had died after being exposed to the extract.
The investigators, who report their findings in the
January 1, 2009, issue of Clinical Cancer Research, a journal of
the American Association for Cancer Research, also teased apart the cell
signaling pathway associated with use of grape seed extract that led to
cell death, or apoptosis. They found that the extract activates JNK, a
protein that regulates the apoptotic pathway.
Grape seed contains antioxidants-substances that
prevent cell damage caused by free radicals, which are highly reactive
molecules that can damage cell function. Beneficial antioxidant effects
have been widely associated with red wine.
While grape seed extract has demonstrated benefits
in a number of laboratory cancer cell lines, including skin, breast,
colon, lung, stomach and prostate cancers, no one had tested the extract
in hematological cancers nor had the precise mechanism for activity been
revealed. (See sidebar on What the Science Says.)
"These results could have implications for the
incorporation of agents such as grape seed extract into prevention or
treatment of hematological malignancies and possibly other cancers,"
said the study's lead author, Xianglin Shi, Ph.D., professor in the
Graduate Center for Toxicology at the University of Kentucky.
What
the Science Says
● Laboratory studies have shown that grape seed contains
antioxidants-substances that prevent cell damage caused by free
radicals, which are highly reactive molecules that can damage
cell function. However, it is still unclear how grape seed might
affect human health.
● Grape seed extract has shown some beneficial antioxidant
effects in preliminary clinical trials. However, few trials have
looked at specific diseases or conditions, and little scientific
evidence is available.
● A study funded by the National Cancer Institute (NCI) found
that grape seed extract did not reduce the hardening of breast
tissue that can occur after radiation therapy for breast cancer.
● NCI is also funding studies evaluating whether grape seed
extract is effective in preventing breast and prostate cancers.
● NCCAM is studying whether the action of grape seed extract
and its components may benefit the heart or have protective
effects in the brain.
Grape Seed Extract May Help
Prevent and Treat Alzheimer's
Emerging research shows a correlation between red wine
consumption and reduced risk of Alzheimer's disease-type
cognitive decline.
Authors of a new NCCAM-funded study in mice found that grape
seed-derived polyphenolicssimilar to that in red
winesignificantly reduced Alzheimer's disease-type cognitive
deterioration.
According to the National Institute on Aging (NIA), Alzheimer's
disease affects nearly 4.5 million Americans and is the most
common form of dementia in the elderly.
Alzheimer's disease is an incurable disease with a slow
progression beginning with mild memory loss and ending with
severe brain damage and death.
While no treatment is proven to stop Alzheimer's disease, some
conventional drugs may limit symptoms for a short period of time
in the early stages of the disease.
"What everyone seeks is an agent that has an effect
on cancer cells but leaves normal cells alone, and this shows that grape
seed extract fits into this category," he said.
Shi adds, however, that the research is not far
enough along to suggest that people should eat grapes, grape seeds, or
grape skin in excess to stave off cancer. "This is very promising
research, but it is too early to say this is chemo-protective."
Hematological cancers leukemia, lymphoma and
myeloma accounted for an estimated 118,310 new cancer cases and almost
54,000 deaths in 2006. This ranks these cancers as the fourth leading
cause of cancer incidence and death in the U.S.
Given that epidemiological evidence shows that
eating vegetables and fruits helps prevent cancer development, Shi and
his colleagues have been studying chemicals known as proanthocyanidins
in fruits that contribute to this effect.
Shi has found that apple peel extract contains
these flavonoids, which have antioxidant activity, and which cause
apoptosis (cell death necessary for new cells and to remove cells whose
DNA has been damaged to the point at which cancerous change is liable to
occur) in several cancer cell lines but not in normal cells. Based on
those studies, and findings from other researchers that grape seed
extract reduces breast tumors in rats and skin tumors in mice, they
looked at the effect of the compound in leukemia cells.
Using a commercially available grape seed extract,
Shi exposed leukemia cells to the extract in different doses and found
the marked effect in causing apoptosis in these cells at one of the
higher doses.
They also discovered that the extract does not
affect normal cells, although they don't know why.
The researchers then used pharmacologic and genetic
approaches to determine how the extract induced apoptosis. They found
that the extract strongly activated the JNK pathway, which then led to
up-regulation of Cip/p21, which controls the cell cycle.
They checked this finding by using an agent that
inhibited JNK, and found that the extract was ineffective. Using a
genetic approach silencing the JNK gene also disarmed grape seed
extract's lethal attack in leukemia cells.
"This is a natural compound that appears to have
relatively important properties," Shi said.
About AACR
The mission of the American Association for Cancer
Research is to prevent and cure cancer. Founded in 1907, AACR is the
world's oldest and largest professional organization dedicated to
advancing cancer research. The membership includes more than 28,000
basic, translational and clinical researchers; health care
professionals; and cancer survivors and advocates in the United States
and 80 other countries. The AACR marshals the full spectrum of expertise
from the cancer community to accelerate progress in the prevention,
diagnosis and treatment of cancer through high-quality scientific and
educational programs. It funds innovative, meritorious research grants.
The AACR publishes five major peer-reviewed
journals: Cancer Research; Clinical Cancer Research; Molecular Cancer
Therapeutics; Molecular Cancer Research; and Cancer Epidemiology,
Biomarkers & Prevention. The AACR's most recent publication and its
sixth major journal, Cancer Prevention Research, is dedicated
exclusively to cancer prevention, from preclinical research to clinical
trials. The AACR also publishes CR, a magazine for cancer survivors and
their families, patient advocates, physicians and scientists. CR
provides a forum for sharing essential, evidence-based information and
perspectives on progress in cancer research, survivorship and advocacy.
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