Chemopreventive and adjuvant therapeutic potential of pomegranate (Punica granatum) for human breast cancer.
Fresh 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 warranted.
Kim
Nam Deuk
ND
Department of Pharmacy, Pusan National University, Korea.
Mehta
Rajendra
R
Yu
Weiping
W
Neeman
Ishak
I
Livney
Talia
T
Amichay
Akiva
A
Poirier
Donald
D
Nicholls
Paul
P
Kirby
Andrew
A
Jiang
Wenguo
W
Mansel
Robert
R
Ramachandran
Cheppail
C
Rabi
Thangaiyan
T
Kaplan
Boris
B
Lansky
Ephraim
E
D015067:17-Hydroxysteroid Dehydrogenases / Q000737:chemistry; D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D001940:Breast / Q000166:cytology / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects*; D018890:Chemoprevention; D017024:Chemotherapy, Adjuvant; D004305:Dose-Response Relationship, Drug; D004967:Estrogens / Q000096:biosynthesis; D005260:Female; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000517:prevention & control; D051379:Mice; D008807:Mice, Inbred BALB C; D009362:Neoplasm Metastasis; D029594:Onagraceae; D008517:Phytotherapy; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D010938:Plant Oils / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D014407:Tumor Cells, Cultured / Q000187:drug effects; D015003:Yeasts / Q000187:drug effects / Q000502:physiology
D000970:Antineoplastic Agents; D004967:Estrogens; D010936:Plant Extracts; D010938:Plant Oils; D015127:9,10-Dimethyl-1,2-benzanthracene; D015067:17-Hydroxysteroid Dehydrogenases; C044256:3 (or 17)-beta-hydroxysteroid dehydrogenase