| More Evidence Shows Grape Skin
Antioxidant Resveratrol Kills Cancer
Rochester researchers showed for the first time that a natural
antioxidant found in grape skins and red wine can help destroy
pancreatic cancer cells by reaching to the cell's core energy
source, or mitochondria, and crippling its function. The study
is published in the March edition of the journal, Advances in
Experimental Medicine and Biology.
The study also showed that when the pancreatic cancer cells were
doubly assaulted -- pre-treated with the antioxidant, resveratrol,
and irradiated -- the combination induced a type of cell death
called apoptosis, an important goal of cancer therapy.
The research has many implications for patients, said lead author
Paul Okunieff, M.D., chief of Radiation Oncology at the James
P. Wilmot Cancer Center at the University of Rochester Medical
Although red wine consumption during chemotherapy or radiation
treatment has not been well studied, it is not "contraindicated,"
Okunieff said. In other words, if a patient already drinks red
wine moderately, most physicians would not tell the patient to
give it up during treatment. Perhaps a better choice, Okunieff
said, would be to drink as much red or purple grape juice as desired.
Yet despite widespread interest in antioxidants, some physicians
are concerned antioxidants might end up protecting tumors. Okunieff's
study showed there is little evidence to support that fear. In
fact, the research suggests resveratrol not only reaches its intended
target, injuring the nexus of malignant cells, but at the same
time protects normal tissue from the harmful effects of radiation.
"Antioxidant research is very active and very seductive
right now," Okunieff said. "The challenge lies in finding
the right concentration and how it works inside the cell. In this
case, we've discovered an important part of that equation. Resveratrol
seems to have a therapeutic gain by making tumor cells more sensitive
to radiation and making normal tissue less sensitive."
Resveratrol is known for its ability to protect plants from bacteria
and fungi. Purified versions have been described in scientific
journals as potential anti-cancer, anti-inflammatory and anti-atherogenic
agents, and for their ability to modulate cell growth. Other well-known
antioxidants derived from natural sources include caffeine, melatonin,
flavonoids, polyphenols, and vitamins C and E.
A flurry of antioxidant studies in recent years has not proven
how and why they work at the cellular level. At the suggestion
of a young scientist in his lab, Okunieff began studying resveratrol
as a tumor sensitizer. That's when they discovered its link to
The discovery is critical because, like the cell nucleus, the
mitochondria contains its own DNA and has the ability to continuously
supply the cell with energy when functioning properly. Stopping
the energy flow theoretically stops the cancer.
Researchers divided pancreatic cancer cells into two groups:
cells treated without resveratrol, or with resveratrol, at a relatively
high dose of 50 mg/ml, in combination with ionizing radiation.
(The resveratrol concentration in red wine can be as high as 30
mg/ml, the study said, and higher doses are expected to be safe
as long as a physician is monitoring.)
They evaluated the mitochondria function of the cells treated
with resveratrol, and also measured apoptosis (cell death), the
level of reactive oxygen species in the cells, and how the cell
membranes responded to the antioxidant.
Laboratory experiments showed that resveratrol:
* Reduced the function of proteins in the pancreatic cancer cell
membranes that are responsible for pumping chemotherapy out of
the cell, making the cells chemo-sensitive.
* Triggered the production of reactive oxygen species (ROS),
which are substances circulating in the human body that have been
implicated in a number of diseases: when ROS is increased, cells
burn out and die.
* Caused apoptosis, which is likely the result of increased ROS.
* Depolarized the mitochondrial membranes, which indicates a
decrease in the cell's potential to function. Radiation alone
does not injure the mitochondrial membrane as much.
The team also wanted to investigate why pancreatic cancer cells
seem to be particularly resistant to chemotherapy. The pancreas,
a gland located deep in the abdomen, produces insulin and regulates
sugar, and pumps or channels powerful digestive enzymes into the
duodenum. This natural pumping process, however, ends up ridding
the needed chemotherapy from cells in the pancreas. But just as
reseveratrol interferes with the cancer cells' energy source,
it also may decrease the power available to pump chemotherapy
out of the cell.
"While additional studies are needed," Okunieff said,
"this research indicates that resveratrol has a promising
future as part of the treatment for cancer."
In the same journal, Okunieff and his group also reviewed why
resveratrol protects normal tissue, and found that antioxidants
can be designed to take advantage of certain biochemical properties
or cellular targets, making them more effective.