Chemico-Biological Interactions 181 (2009) 85–94 Contents lists available at ScienceDirect Chemico-Biological Interactions journal homepage: www.elsevier.com/locate/chembioint Relationship correlation of antioxidant and antiproliferative capacity of Cyperus rotundus products towards K562 erythroleukemia cells Soumaya Kilani-Jaziri a , Aicha Neffati a , Ilef Limem a , Jihed Boubaker a , Ines Skandrani a , Mohamed Ben Sghair a , Ines Bouhlel a , Wissem Bhouri a , Anne Marie Mariotte d , Kamel Ghedira a , Marie-Genviève Dijoux Franca c , Leila Chekir-Ghedira a,b,∗ a Unité de Pharmacognosie/Biologie Moléculaire 99/UR/07-03, Faculté de Pharmacie, Rue Avicenne 5000 Monastir, Tunisia b Laboratoire de Biologie Cellulaire et Moléculaire, Faculté de Médecine Dentaire, Rue Avicenne, Monastir 5000, Tunisia c Laboratoire de Botanique, Pharmacognosie et Phytothérapie, UMR CNRS 5557 Ecologie Microbienne, Institut des Sciences Pharmaceutiques et Biologiques, Faculté de Pharmacie Université Claude Bernard, Bâtiment Nétien-8 Avenue Rockefeller 69373, Lyon cedex 08, France d Département de Pharmaco-Chimie Moléculaire, UMR 5063 CNRS-UJF, UFR de Pharmacie, Faculté de Pharmacie-Domaine de la Merci, 38706 La Tronche cedex, Grenoble, France article info Article history: Received 22 September 2008 Received in revised form 25 April 2009 Accepted 27 April 2009 Available online 14 May 2009 Keywords: Cyperus rotundus Flavonoids Polyphenol derivatives Plasmid DNA damage Antioxidant capacity Apoptosis abstract A Total Oligomers Flavonoids (TOFs) and ethyl acetate extracts of Cyperus rotundus were analyzed, in vitro, for their antioxidant activity using several biochemical assays: the xanthine (X)/xanthine oxidase (XO), the lipid peroxidation induced by H 2 O 2 in K562 human chronic myelogenous leukemia cells and the DNA damage in pKS plasmid DNA assay induced by H 2 O 2 /UV-photolysis and for their apoptotic effect. TOF and ethyl acetate extracts were found to be efficient in inhibiting xanthine oxidase with IC 50 values of 240 and 185 g/ml and superoxide anion with IC 50 values of 150 and 215 g/ml, respectively. Also, all the extracts tested were effective in reducing the production of thiobarbituric acid reactive substances (TBARS) and were able to protect against H 2 O 2 /UV-photolysis induced DNA damage. The highest activity, measured as equivalents of MDA concentration, was observed in the ethyl acetate extract (MDA = 2.04 nM). In addition, the data suggest that only TOF enriched extract exerts growth inhibition on K562 cells through apoptosis induction. Therefore, these extracts were subjected to further separation by chromatographic meth- ods. Thus, three major compounds (catechin, afzelechin and galloyl quinic acid) were isolated from the TOF enriched extract and five major compounds (luteolin, ferulic acid, quercetin, 3-hydroxy, 4-methoxy- benzoic acid and 6,7-dimethoxycoumarin) from ethyl acetate extract. Their structures were determined by spectroscopic data analysis and comparison with the literature. In addition, we evaluate the biological activities of the catechin, ferulic acid and luteolin. This investigation has revealed that the luteolin was the most active in reducing the production of TBARS (MDA = 1.5 nM), inhibiting significantly the prolif- eration of K562 cells (IC 50 = 25 g/ml) and protecting against H 2 O 2 /UV-photolysis induced DNA damage. In conclusion, the study reveals that the ability of C. rotundus to inhibit the enzyme xanthine oxidase (XO), the lipid peroxidation and to exert apoptotic effect, may explain possible mechanisms by which C. rotundus exhibits its health benefits. © 2009 Elsevier Ireland Ltd. All rights reserved. 1. Introduction Apoptosis is a cell suicide program that has been conserved through the evolution. Induction of apoptosis thus is a highly desir- able mode as a chemotherapeutic as well as a chemopreventive strategy for cancer control. Recently, interest has focused on the manipulation of apoptotic processes in the treatment and pre- ∗ Corresponding author at: Laboratoire de Biologie Cellulaire et Moléculaire, Fac- ulty of Dental Medicine, Rue Avicenne, Monastir 5019, Tunisia. Tel.: +216 97 316 282; fax: +216 73 461 150. E-mail addresses: leila.chekir@laposte.net, lchekir@yahoo.fr (L. Chekir-Ghedira). vention of cancer. Thus, much effort has been directed toward the search for compounds or herbs that influence apoptosis and their mechanism of action. In fact, there has been increasing real- ization, in recent years, that several plant derived polyphenolic compounds may possess antioxidant, anticancer and apoptosis inducing properties. To date, many anticancer drugs used in chemotherapeutic treatments developed resistance and side effects [1,2]. In a program to find new natural sources of antioxidative and antiproliferative agents from Tunisian medicinal plants, we studied the efficiency of extracts and compounds from Cyperus rotun- dus. C. rotundus Linn, a sedge of the Cyperaceae family, is widely distributed in the Mediterranean basin areas. This plant, which 0009-2797/$ – see front matter © 2009 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.cbi.2009.04.014