Chemopreventive and adjuvant therapeutic potential of pomegranate (Punica granatum) for human breast cancer.

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Breast Cancer Res Treat. 2002 Feb;71(3):203-17
Chemopreventive and adjuvant therapeutic potential of pomegranate (Punica granatum) for human breast cancer.

Kim ND, Mehta R, Yu W, Neeman I, Livney T, Amichay A, Poirier D, Nicholls P, Kirby A, Jiang W, Mansel R, Ramachandran C, Rabi T, Kaplan B, Lansky E.

Department of Pharmacy, Pusan National University, Korea.
organically grown pomegranates (Punica granatum L.) of the Wonderful
cultivar were processed into three components: fermented juice, aqueous
pericarp extract and cold-pressed or supercritical CO2-extracted seed
oil. Exposure to additional solvents yielded polyphenol-rich fractions
('polyphenols') from each of the three components. Their actions, and
of the crude whole oil and crude fermented and unfermented juice
concentrate, were assessed in vitro for possible chemopreventive or
adjuvant therapeutic potential in human breast cancer. The ability to
effect a blockade of endogenous active estrogen biosynthesis was shown
by polyphenols from fermented juice, pericarp, and oil, which inhibited
aromatase activity by 60-80%. Fermented juice and pericarp polyphenols,
and whole seed oil, inhibited 17-beta-hydroxysteroid dehydrogenase Type
1 from 34 to 79%, at concentrations ranging from 100 to 1,000 microg/ml
according to seed oil >> fermented juice polyphenols >
pericarp polyphenols. In a yeast estrogen screen (YES) lyophilized
fresh pomegranate juice effected a 55% inhibition of the estrogenic
activity of 17-beta-estradiol; whereas the lyophilized juice by itself
displayed only minimal estrogenic action. Inhibition of cell lines by
fermented juice and pericarp polyphenols was according to
estrogen-dependent (MCF-7) >> estrogen-independent (MB-MDA-231)
> normal human breast epithelial cells (MCF-10A). In both MCF-7 and
MB-MDA-231 cells, fermented pomegranate juice polyphenols consistently
showed about twice the anti-proliferative effect as fresh pomegranate
juice polyphenols. Pomegranate seed oil effected 90% inhibition of
proliferation of MCF-7 at 100 microg/ml medium, 75% inhibition of
invasion of MCF-7 across a Matrigel membrane at 10 microg/ml, and 54%
apoptosis in MDA-MB-435 estrogen receptor negative metastatic human
breast cancer cells at 50 microg/ml. In a murine mammary gland organ
culture, fermented juice polyphenols effected 47% inhibition of
cancerous lesion formation induced by the carcinogen
7,12-dimethylbenz[a]anthracene (DMBA). The findings suggest that
clinical trials to further assess chemopreventive and adjuvant
therapeutic applications of pomegranate in human breast cancer may be