A Diet Rich in Fruits and Vegetables may protect against Prostate Cancer .

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Since there were recent questions about diet, this information may be

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Credit goes to Food Industry Environmental Network for this release.

Both the Case Western News Release and the Journal Abstract follow this

summary.

NUTRITION, FRUITS AND VEGETABLES, MEDICAL AND RISK ASSESSMENT

* A Diet Rich in Fruits and Vegetables may protect against Prostate

Cancer, according a study, titled " Up-regulation of insulin-like growth

factor binding protein-3 by apigenin leads to growth inhibition and

apoptosis of 22Rv1 xenograft in athymic nude mice, " which was published

online on October 17 in the Journal of the Federation of American

Societies for Experimental Biology by researchers with Case Western

Reserve University School of Medicine Department of Urology in

Cleveland, Ohio and the University of Pittsburgh - According to an

accompanying October 20 Case Western News Release, titled " Flavonoids

may inhibit prostate cancer " " ... Previous studies have suggested that

increased intake of flavonoids which are common in fruits and vegetables

may be associated with a reduced risk of prostate cancer, according to

Sanjay Gupta, Ph.D., an assistant professor in the Case School of

Medicine Department of Urology. Apigenin is a plant flavonoid commonly

found in fruits and vegetables, as well as herbs, including chamomile,

lemon balm, perilla and parsley ... In the study, Gupta and his team

orally fed apigenin to mice two weeks before implanting a prostate

tumor, then continuing the feedings for eight weeks. In a second

protocol, apigenin was fed to mice two weeks after tumor implantation.

The first protocol mimicked prevention regimens, while the second

followed therapeutic regimens for cancer. In both cases, the apigenin

slowed tumor growth and did not appear to cause any adverse side effects

such as weight gain or changes in diet, which is common in patients who

undergo chemotherapy treatments. Apigenin also resulted in a decrease in

IGF-1 (insulin-like growth factor) levels, which are associated with an

increased risk of breast, prostate, colorectal and lung cancers, as well

as a significant increase in IGFBP-3 (insulin-like growth factor binding

protein) levels, which is associated with a decreased risk for these

same cancers. The effect impacts the survival of prostate cancer by

triggering cell self-destruction. 'Apigenin may prove useful in the

prevention and therapy of prostate cancer by shutting off the IGF

signaling that leads to prostate cancer cell growth and/or development,'

Gupta said. 'Our findings suggest that apigenin could be developed as a

promising agent against prostate cancer,' Gupta said. 'The next step is

to evaluate apigenin action on other molecular pathways which have

relevance to prostate cancer ... " - The abstract of the FASEB Journal

article is posted at

http://www.fasebj.org/cgi/content/abstract/05-3740fjev1 - The Case

Western news release is posted at

http://www.eurekalert.org/pub_releases/2005-10/cwru-fmi102005.php -

Reprint requests and questions may be directed to Sanjay Gupta, Ph.D.,

Assistant Professor, Case Western Reserve University, School of

Medicine, Department of Urology at ; fax: ;

e-mail: Sanjay.Gupta@...

http://www.eurekalert.org/pub_releases/2005-10/cwru-fmi102005.php

Public release date: 20-Oct-2005

Contact: Stamatis

.Stamatis@...

Case Western Reserve University

Flavonoids may inhibit prostate cancer

Eating a diet rich in fruits and vegetables could be a good defense

against prostate cancer, according to a Case Western Reserve University

study published in the October online issue of the Federation of

American Societies for Experimental Biology Journal.

Previous studies have suggested that increased intake of flavonoids

which are common in fruits and vegetables may be associated with a

reduced risk of prostate cancer, according to Sanjay Gupta, Ph.D., an

assistant professor in the Case School of Medicine Department of

Urology. Apigenin is a plant flavonoid commonly found in fruits and

vegetables, as well as herbs, including chamomile, lemon balm, perilla

and parsley.

" Flavonoids have aroused considerable interest recently because of their

potential beneficial effects on human health, and have reported to have

antiviral, anti-allergic, antiplatelet, anti-inflammatory, antitumor and

antioxidant activities, " Gupta said. " Apigenin has been shown to lower

inflammation and oxidative stress, and exerts growth inhibitory effects

on cancer cells. "

In the study, Gupta and his team orally fed apigenin to mice two weeks

before implanting a prostate tumor, then continuing the feedings for

eight weeks. In a second protocol, apigenin was fed to mice two weeks

after tumor implantation.

The first protocol mimicked prevention regimens, while the second

followed therapeutic regimens for cancer.

In both cases, the apigenin slowed tumor growth and did not appear to

cause any adverse side effects such as weight gain or changes in diet,

which is common in patients who undergo chemotherapy treatments.

Apigenin also resulted in a decrease in IGF-1 (insulin-like growth

factor) levels, which are associated with an increased risk of breast,

prostate, colorectal and lung cancers, as well as a significant increase

in IGFBP-3 (insulin-like growth factor binding protein) levels, which is

associated with a decreased risk for these same cancers. The effect

impacts the survival of prostate cancer by triggering cell

self-destruction.

" Apigenin may prove useful in the prevention and therapy of prostate

cancer by shutting off the IGF signaling that leads to prostate cancer

cell growth and/or development, " Gupta said.

" Our findings suggest that apigenin could be developed as a promising

agent against prostate cancer, " Gupta said. " The next step is to

evaluate apigenin action on other molecular pathways which have

relevance to prostate cancer. "

Gupta's colleagues contributing to the study included Sanjeev Shukla,

Ph.D.; T. MacLennan, M.D.; Pingfu Fu, Ph.D.; I. Resnick,

M.D.; from Case Western Reserve University and University Hospitals of

Cleveland, and Anil Mishra, Ph.D. from University of Pittsburgh.

###

*********************

http://www.fasebj.org/cgi/content/abstract/05-3740fjev1

Published Online on October 17, 2005

The FASEB Journal Express Article doi:10.1096/fj.05-3740fje

Up-regulation of insulin-like growth factor binding protein-3 by

apigenin leads to growth inhibition and apoptosis of 22Rv1 xenograft in

athymic nude mice

Sanjeev Shukla, Anil Mishra, Pingfu Fu, T. MacLennan, I.

Resnick, and Sanjay Gupta

E-mail contact: sanjay.gupta@...

Epidemiological studies suggest that increased intake of fruits and

vegetables may be associated with a reduced risk of prostate cancer.

Apigenin (4', 5, 7,-trihydroxyflavone), a common dietary flavonoid

abundantly present in fruits and vegetables, has shown remarkable

anti-proliferative effects against various malignant cell lines.

However, the mechanisms underlying these effects remain to be

elucidated.

We investigated the in vivo growth inhibitory effects of apigenin on

androgen-sensitive human prostate carcinoma 22Rv1 tumor xenograft

subcutaneously implanted in athymic male nude mice.

Apigenin was administered to mice by gavage at doses of 20 and 50

µg/mouse/day in 0.2 ml of a vehicle containing 0.5% methyl cellulose and

0.025% Tween 20 in two different protocols. In the first protocol,

apigenin was administered for 2 wk before inoculation of tumor and was

continued for 8 wk, resulting in significant inhibition of tumor volume

by 44 and 59% (P<0.002 and 0.0001), and wet weight of tumor by 41 and

53% (P<0.05), respectively.

In the second protocol, administration of apigenin began 2 wk after

tumor inoculation and continued for 8 wk; tumor volume and wet weights

of tumor were reduced by 39 and 53% (P<0.01 and 0.002) and 31 and 42%

(P<0.05), respectively.

The tumor inhibitory effect of apigenin was more pronounced in the first

protocol of extended treatment, which was associated with increased

accumulation of human IGFBP-3 in mouse serum along with significant

increase in IGFBP-3 mRNA and protein expression in tumor xenograft.

Apigenin intake by these mice also resulted in simultaneous decrease in

serum IGF-I levels and induction of apoptosis in tumor xenograft.

Importantly, tumor growth inhibition, induction of apoptosis, and

accumulation of IGFBP-3 correlated with increasing serum and tumor

apigenin levels.

In both studies, animals did not exhibit any signs of toxicity or

reduced food consumption. In cell culture studies, apigenin treatment

resulted in cell growth inhibition and induction of apoptosis, which

correlated with increased accumulation of IGFBP-3 in culture medium and

cell lysate.

These effects were associated with significant reduction in IGF-I

secretion; inhibition of IGF-I-induced cell cycle progression and

insulin receptor substrate-1 (IRS-1) tyrosine phosphorylation, along

with an increase in sub-G1 peak by apigenin.

Further, treatment of cells with IGFBP-3 antisense oligonucleotide

reversed these effects and attenuated apigenin-mediated inhibition of

IRS-1 phosphorylation conferring inhibitory effects of apigenin on

IGF-signaling.

This study presents the first evidence that the in vitro and in vivo

growth inhibitory effects of apigenin involve modulation of IGF-axis

signaling in prostate cancer.

Key words: insulin-like growth factor-I • insulin-like growth factor

receptor-1 • insulin receptor substrate-1

end of abstract