title: Anti-proliferative activity and protection against oxidative DNA damage by punicalagin isolated from pomegranate husk.
abstract: Ellagitannins are the most abundant polyphenols in pomegranate (Punica granatum) husk and contribute greatly towards its biological properties. A pre-enriched pomegranate husk powder was extracted with water and then further purified by an Amberlite XAD-16 column. Punicalagin (PC) anomers were eluted using a gradient of methanol and water. Fractions eluted with 20% and 25% methanol yielded 1.08 g of light brown powder (purity > 97%) from a total of 40 g of extract. This fraction was identified as PC by HPLC-UV using reference compounds and confirmed by FTICR-MS analysis. PC (10-40 µM) was found to significantly inhibit oxidative DNA products, about 70% inhibition at 40 µM (p=0.0017), resulting from Cu2+-catalyzed redox cycling of 4-hydroxy-17β-estradiol as analyzed by32P-postlabeling. Evidence of high antioxidant activity of PC was also obtained based on ORAC assay (1556±79 µmol of TE/g), as well as by 2,2'-azino-bis (3-ethylbenzthiazoline-6-sulphonic acid) (ABTS)-, 2,2-diphenyl-1-picrylhydrazyl (DPPH)-, hydrogen peroxide (H2O2) scavenging and ferrous ion-chelating activities (IC50=1.1, 17.1, 24 and 45.4 µg/ml, respectively). Further, PC exhibited strong anti-proliferative activity against the human lung, breast and cervical cancer cell lines. Together, these data suggest that PC can be isolated in its purified form by simple column chromatography, inhibits oxidative DNA damage and possesses high anti-proliferative activity.
authors.affiliation: James Graham Brown Cancer Center, University of Louisville, Louisville, KY 40202, USA.
authors.forename: Farrukh
authors.initials: F
authors.lastname: Aqil
authors.forename: Radha
authors.initials: R
authors.lastname: Munagala
authors.forename: Manicka V
authors.initials: MV
authors.lastname: Vadhanam
authors.forename: Hina
authors.initials: H
authors.lastname: Kausar
authors.forename: Jeyaprakash
authors.initials: J
authors.lastname: Jeyabalan
authors.forename: David J
authors.initials: DJ
authors.lastname: Schultz
authors.forename: Ramesh C
authors.initials: RC
authors.lastname: Gupta
keywords: 32P-postlabeling; Antioxidant activity; Antiproliferative activity; Oxidative DNA damage; Punica granatum; Punicalagin