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.

While grape seed extract has shown activity 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.

"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 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, ranking
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 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.

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
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Special conferences throughout the year present novel data across a wide
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