title: Punicalagin and ellagic acid demonstrate antimutagenic activity and inhibition of benzo[a]pyrene induced DNA adducts.
abstract: Punicalagin (PC) is an ellagitannin found in the fruit peel of Punica granatum. We have demonstrated antioxidant and antigenotoxic properties of Punica granatum and showed that PC and ellagic acid (EA) are its major constituents. In this study, we demonstrate the antimutagenic potential, inhibition of BP-induced DNA damage, and antiproliferative activity of PC and EA. Incubation of BP with rat liver microsomes, appropriate cofactors, and DNA in the presence of vehicle or PC and EA showed significant inhibition of the resultant DNA adducts, with essentially complete inhibition (97%) at 40 μ M by PC and 77% inhibition by EA. Antimutagenicity was tested by Ames test. PC and EA dose-dependently and markedly antagonized the effect of tested mutagens, sodium azide, methyl methanesulfonate, benzo[a]pyrene, and 2-aminoflourine, with maximum inhibition of mutagenicity up to 90 percent. Almost all the doses tested (50-500 μ M) exhibited significant antimutagenicity. A profound antiproliferative effect on human lung cancer cells was also shown with PC and EA. Together, our data show that PC and EA are pomegranate bioactives responsible for inhibition of BP-induced DNA adducts and strong antimutagenic, antiproliferative activities. However, these compounds are to be evaluated in suitable animal model to assess their therapeutic efficacy against cancer.
authors.affiliation: Department of Agricultural Microbiology, Aligarh Muslim University, Aligarh 202002, India ; James Graham Brown Cancer Center, University of Louisville, Louisville, KY 40202, USA.
authors.forename: Maryam
authors.initials: M
authors.lastname: Zahin
authors.affiliation: Department of Agricultural Microbiology, Aligarh Muslim University, Aligarh 202002, India.
authors.forename: Iqbal
authors.initials: I
authors.lastname: Ahmad
authors.affiliation: James Graham Brown Cancer Center, University of Louisville, Louisville, KY 40202, USA ; Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY 40202, USA.
authors.forename: Ramesh C
authors.initials: RC
authors.lastname: Gupta
authors.affiliation: James Graham Brown Cancer Center, University of Louisville, Louisville, KY 40202, USA ; Department of Medicine, University of Louisville, Delia Baxter II, Room 304B, 580 S. Preston Street, Louisville, KY 40202, USA.
authors.forename: Farrukh
authors.initials: F
authors.lastname: Aqil
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage; D001564:Benzo(a)pyrene / Q000494:pharmacology; D018736:DNA Adducts / Q000187:drug effects*; D004249:DNA Damage / Q000187:drug effects; D004610:Ellagic Acid / Q000008:administration & dosage* / Q000737:chemistry; D006801:Humans; D047348:Hydrolyzable Tannins / Q000008:administration & dosage* / Q000737:chemistry; D029561:Lythraceae / Q000737:chemistry; D016296:Mutagenesis / Q000187:drug effects; D010936:Plant Extracts / Q000008:administration & dosage* / Q000737:chemistry; D051381:Rats; D012486:Salmonella typhimurium / Q000187:drug effects
chemical_list: D000975:Antioxidants; D018736:DNA Adducts; D047348:Hydrolyzable Tannins; D010936:Plant Extracts; D004610:Ellagic Acid; D001564:Benzo(a)pyrene; C115642:punicalagin