title: Pomegranate ellagitannin-derived compounds exhibit antiproliferative and antiaromatase activity in breast cancer cells in vitro.
abstract: Estrogen stimulates the proliferation of breast cancer cells and the growth of estrogen-responsive tumors. The aromatase enzyme, which converts androgen to estrogen, plays a key role in breast carcinogenesis. The pomegranate fruit, a rich source of ellagitannins (ET), has attracted recent attention due to its anticancer and antiatherosclerotic properties. On consumption, pomegranate ETs hydrolyze, releasing ellagic acid, which is then converted to 3,8-dihydroxy-6H-dibenzo[b,d]pyran-6-one ("urolithin") derivatives by gut microflora. The purpose of this study was to investigate the antiaromatase activity and inhibition of testosterone-induced breast cancer cell proliferation by ET-derived compounds isolated from pomegranates. A panel of 10 ET-derived compounds including ellagic acid, gallagic acid, and urolithins A and B (and their acetylated, methylated, and sulfated analogues prepared in our laboratory) were examined for their ability to inhibit aromatase activity and testosterone-induced breast cancer cell proliferation. Using a microsomal aromatase assay, we screened the panel of ET-derived compounds and identified six with antiaromatase activity. Among these, urolithin B (UB) was shown to most effectively inhibit aromatase activity in a live cell assay. Kinetic analysis of UB showed mixed inhibition, suggesting more than one inhibitory mechanism. Proliferation assays also determined that UB significantly inhibited testosterone-induced MCF-7aro cell proliferation. The remaining test compounds also exhibited antiproliferative activity, but to a lesser degree than UB. These studies suggest that pomegranate ET-derived compounds have potential for the prevention of estrogen-responsive breast cancers.
authors.affiliation: Beckman Research Institute of the City of Hope, Duarte, California, USA.
authors.forename: Lynn S
authors.initials: LS
authors.lastname: Adams
authors.forename: Yanjun
authors.initials: Y
authors.lastname: Zhang
authors.forename: Navindra P
authors.initials: NP
authors.lastname: Seeram
authors.forename: David
authors.initials: D
authors.lastname: Heber
authors.forename: Shiuan
authors.initials: S
authors.lastname: Chen
mesh_terms: D001141:Aromatase / Q000187:drug effects / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D005260:Female; D006801:Humans; D047348:Hydrolyzable Tannins / Q000494:pharmacology*; D029561:Lythraceae / Q000737:chemistry*; D010936:Plant Extracts / Q000494:pharmacology*
chemical_list: D047348:Hydrolyzable Tannins; D010936:Plant Extracts; C013515:ellagitannin; D001141:Aromatase