New Study Confirms Red Wine Antioxidant Kills Cancer
Researchers pinpoint how resveratrol induces
pancreatic cancer cell death
March
26, 2008 - 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
Center.
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 mitochondria.
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.
Editors Notes:
The National Institute of Allergy and Infectious
Diseases funded the research through a URMC program called the Center
for Medical Countermeasures Against Radiation. Co-authors on the studies
are: Weimin Sun, Wei Wang, Jung Kim, Peter Keng, Shanmin Yang, Hengshan
Zheng, Chaomei Liu, Lurong Zhang, Jacqueline P. Williams, Steven Swarts
and Amy K. Huser. All are from the Department of Radiation Oncology,
University of Rochester Medical Center.
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March
26, 2008 - 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.