Two recent studies suggest that naturally occurring antiangiogenic
molecules present in black raspberries and licorice may have a role in
preventing some types of cancer. In the first study published in the
journal Cancer Prevention(1), researchers at the Ohio State
Comprehensive Cancer Center found that anthocyanins, a class of
flavonoids present in many types of berries, as well as red wine,
inhibited tumor growth and angiogenesis, and stimulated cancer cell
death in the experimental rats treated with a potent esophageal
Dr. Gary D. Stoner and colleagues fed rats an anthocyanin-rich extract
of black raspberries and found that the extract was nearly as effective
in preventing esophageal cancer in rats as whole black raspberries
containing the same concentration of anthocyanins. In addition to
reducing markers of inflammation and cell proliferation in the
esophagus, the anthocyanins suppressed the expression of the angiogenic
factors vascular endothelial growth factor (VEGF) and hypoxia-inducible
factor-1alpha (HIF-1alpha). The VEGF protein is a primary stimulator of
tumor angiogenesis, and upregulation of HIF-1alpha is considered an
initiating step in the angiogenesis cascade. Inhibitors of VEGF are
already used, as drugs, to treat a variety of cancers as well as
blinding disorders. According to the Angiogenesis Foundation, the
opportunity to utilize dietary sources of naturally-occurring
angiogenesis inhibitors to modify or prevent disease is an important
new frontier for the angiogenesis field.
"Now that we know the
anthocyanins in berries are almost as active as whole berries
themselves, we hope to be able to prevent cancer in humans using a
standardized mixture of anthocyanins," said Dr. Stoner. "The goal is to
potentially replace whole berry powder with its active components and
then figure out better ways to deliver these components into tissues to
increase their uptake and effectiveness. Ultimately, we hope to test
the anthocyanins for effectiveness in multiple organ sites in humans.”
In the second study related to dietary antiangiogenesis, researchers at
Vanderbilt University Medical Center showed that inhibiting an enzyme
called 11β-hydroxysteroid dehydrogenase type 2 (11βHSD2) by treatment
with a natural compound found in licorice prevents colorectal cancer
progression in mice. The study was published in the April issue of the
Journal of Clinical Investigation(2).
The Vanderbilt researchers examined expression of 11βHSD2 in human
colon polyps and in the colons of mice predisposed to colon cancer.
They found that 11βHSD2 was increased in polyps found in both mice and
humans and correlated with COX-2 expression and activity. They then
inhibited 11βHSD2 with glycyrrhizic acid, the main sweet-tasting
component of licorice, and also by silencing the gene for 11βHSD2. Both
treatments inhibited the production of prostaglandin E2 and prevented
the development of polyps (adenomas) and tumor growth and metastasis.
Because 11βHSD2, which modulates the inflammatory enzyme COX2-, is
highly expressed only in kidney and colon, blocking the enzyme produces
effects specific to those tissues.
"Since studies here and
elsewhere have shown the importance of COX-2 and colonic
carcinogenesis, we postulated that maybe one of the mechanisms by which
the normal colon might prevent excessive expression of COX-2 is by
11βHSD2," said Dr. Raymond Harris, the Ann and Roscoe R. Robinson
Professor of Nephrology of Vanderbilt University Department of
Medicine, and an author on the study.
Licorice, Dr. Harris noted, has
been used as a nutraceutical for thousands of years for ailments
ranging from coughs to constipation. In addition to inhibiting COX-2
through 11βHSD2, licorice also contains isoliquiritin, a flavonoid that
has been shown to inhibit angiogenesis, vascular endothelial cell
proliferation and capillary formation.
By Roderick Smith, M.S.
References: 1. Wang L-S, Hecht SS, Carmella SG, et al. Anthocyanins in black raspberries prevent esophageal tumors in rats. Cancer Prev Res 2009;2(1):84-93.
2. Zhang M-Z, Xu J, Yao B, et al. Inhibition of 11b--hydroxysteroid dehydrogenase type II selectively blocks the tumor COX-2 pathway and suppresses colon carcinogenesis in mice and humans. J Clin Invest 2009;119:876-885.