Components of fruit offer protection from skin cancer

Charles Miller 4amiller at bellsouth.net
Fri Nov 7 21:33:55 EST 2003

Fruits Offer Powerful Protection From Skin Cancer
10/29/2003 -- Fruits contain a number of vitamins and minerals that are used
as supplements to treat everyday illnesses. Now, research suggests that
common fruit extracts may have significant clinical benefits in decreasing
risk for skin cancer. These studies were presented at the American
Association for Cancer Research Second Annual International Conference on
Frontiers in Cancer Prevention Research.

"The incidence of skin cancer is rising faster than any other solid tumor in
the United States. It is critical that we develop novel approaches to both
primary and secondary prevention of what appears to be becoming an
epidemic," said David Alberts, M.D., of the University of Arizona.

"We are pleased to see numerous studies exploring the therapeutic value of
topically-applied natural ingredients that people can begin incorporating
into everyday life and may enhance the activity of standard sunscreens."

Pomegranate Fruit Extract is a Novel Agent for Cancer Chemoprevention:
Studies in Mouse Skin (Abstract 1547)

The search for novel anti-cancer therapies is ongoing, especially in the
area of skin cancer, which is the most frequently diagnosed malignancy in
the United States. According to researchers from the University of
Wisconsin, one promising agent against skin cancer may have been found in
the extract of the pomegranate fruit.

Pomegranate fruit extract (PFE), from the tree Punica granatum, contains
several polyphenols and anthocyanidins (pigment that gives certain fruits
their dark red colors), the antioxidant activity of which is higher than
that of red wine and green tea. In this study, researchers evaluated
pomegranate's anti-skin tumor effects by comparing topical application of
pomegranate extract on neonatal mice (CD-1) against TPA-induced markers
(12-0-tetradecanoylphorbol-13-acetate), a strong promoter of chemically
induced skin cancer. Applying pomegranate extract (2 mg/mouse) onto the skin
of neonatal mice 30 minutes prior to TPA (3.2 µmole/mouse) application
significantly inhibited TPA-mediated increases in skin edema and
hyperplasia. TPA is an irritant and inflammatory agent that is widely used
as a tumor promoter on the skin of mice.

Researchers also assessed the effect of skin application of pomegranate
extract on TPA-induced skin tumor promotion. The animals pretreated with
pomegranate extract showed substantially reduced tumor incidence and lower
tumor body burden. In the TPA treated group, all mice developed tumors at 16
weeks, whereas only 30 percent of the mice treated with pomegranate extract
exhibited tumors at that point.

"For the first time, we have clear evidence that pomegranate extract
possesses anti-skin-tumor-promoting effects," said Dr. Farrukh Afaq, of the
University of Wisconsin, and lead investigator of the study.

"With such a variety of pathways inhibited by the topical application of the
natural supplement, we are confident of its therapeutic value and hope it
will translate to other models."

According to the researchers, because pomegranate is capable of inhibiting
conventional as well as novel biomarkers of TPA-induced tumors, it may
possess chemopreventive activity in a wide range of tumor models. To
determine the potential value of pomegranate, researchers will pursue an
in-depth study to define its active agent(s).

Chemoprevention of Multiple Ultraviolet B-Mediated Damages in SKH-1 Hairless
Mouse Skin by Grape Polyphenol Resveratrol: The Underlying Mechanism
(Abstract 1489) 

Knowing that the greater public will never stay far from the beach,
researchers are constantly searching for novel approaches to manage risk
factors for skin cancer, including damage from frequent exposure to solar
ultraviolet (UV) radiation, particularly its UVB component. In this study,
resveratrol, an antioxidant in grapes and red wines, was studied to
determine its chemopreventive potential against UVB-mediated skin damage.

As frequent UVB radiation increases skin cancer risk, researchers evaluated
the effect of topical application of resveratrol (10 µmole/mouse/0.2 ml
acetone) on multiple UVB (seven consecutive exposures in 7 days)
exposure-mediated damages in the skin of SKH-1 hairless mice.

Researchers evaluated resveratrol's influence on survivin, which is involved
in the control of cell division, and is a structurally unique member of the
apoptosis inhibitors protein family. Survivin is overexpressed in most human
cancers, but absent in normal adult tissues, and is considered a promising
therapeutic target for novel anticancer therapies. Results of the study
showed that resveratrol treatment significantly decreased UVB
exposure-mediated up-regulation in the mRNA levels and protein expression of

"We're pleased to see that resveratrol is able to modulate multiple
signaling in the cells, which actually protects the skin cells from damages
that may lead to the development of cancer," said Dr. Nihal Ahmad, of the
University of Wisconsin, and lead author of the study. "Further study should
continue to support the argument to incorporate this agent into skin care
products and regular diets, through the moderate consumption of grapes and
red wine."

Resveratrol significantly inhibited UVB-mediated increases in skin thickness
and edema; epidermal cyclooxygenase (COX-2); ornithine decarboxylase (ODC)
enzyme and protein levels; and protein levels of proliferating cell nuclear
antigen (PCNA), all of which are established markers of tumor promotion.
Resveratrol also further stimulated a UVB-mediated increase in p53 protein
levels and was found to inhibit UVB exposure-mediated increases in cell
cycle promoting signals including the activation of cell division.

Modulation of Ultraviolet Radiation B Induced Wnt-Signaling by Perillyl
Alcohol in Human Keratinocytes (Abstract 1385)

Perillyl alcohol (PEOH) is a food additive and a compound found naturally in
tart cherries, mint and citrus fruits, such as orange peel. Evidence has
shown that this class can inhibit the growth of many cancers and
pre-cancerous lesions by helping rid the body of cancer-causing chemicals or
by interfering with signals that cause rapid cell division. Researchers in
this study determined that the compound maintains its chemopreventive
effects against skin cancer.

"Our research has documented that perillyl alcohol is a potent in vivo
(living cells) inhibitor of both UVB-induced non-melanoma and melanoma in a
transgenic animal model," said Janine Einspahr, Ph.D., of the Arizona Cancer
Center in Tucson, and lead author of the study.

"We are confident that further research will garner results that support
these findings in human models. Phase I and Phase II studies of
topically-administered perillyl alcohol have been initiated at the Arizona
Cancer Center," she added.

In the study, human keratinocytes (skin cells) were treated for 24 hours
with .43 millimolars of PEOH, followed by exposure to 250 millijoules per
cm2 of ultraviolet B radiation (UVB). RNA was isolated for analysis
immediately following UVB exposure, as well as at half, two, six and 24
hours. As compared to untreated cells, expression of 5,533 genes was notably
altered (greater than two fold) with UVB, and 5,837 genes with UVB and PEOH.

Wnt-inhibitory factor-1 (WIF-1) and the Dvl inhibitory protein (IDAX)
prevent activation of Wnt responsive genes. UVB alone suppressed WIF-1
expression as much as five fold at two hours, while UVB and PEOH increased
expression as much as two and a half fold at the six hour time point.
Similarly, UVB alone suppressed IDAX expression as much as three fold at two
hours, while UVB and PEOH increased expression as much as nine fold
immediately following exposure. The Wnt responsive gene, c-myc, was
unchanged with UVB, while UVB and PEOH suppressed expression as much as
seven fold at two hours.

The Wnt signaling pathway helps regulate cell structure, movement and
growth. Activation of the pathway requires the ligand to bind to a frizzled
receptor (the Wnt signal lead receptor). This stimulates the cytoplasmic
protein, disheveled (Dvl), one of the multi-module proteins working in the
pathway. As a result, accumulated catenins, or protein mutations, situate
themselves in the nucleus of the cell. This translocation leads to the
transcription of Wnt targeted genes, such as c-myc, causing cancer.

Skin cancer is the most common cancer, with more than 1.3 million new cases
expected in 2003. Additionally, the American Cancer Society estimates that
in 2003, there will be 54,200 new cases of melanoma, and about 7,600 people
will die of this disease.

Source: American Association for Cancer Research 


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