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Planta Med 2010; 76(6): 589-594
DOI: 10.1055/s-0029-1240604
Pharmacology
Original Papers
© Georg Thieme Verlag KG Stuttgart · New York

Comparative Antioxidant, Prooxidant and Cytotoxic Activity of Sigmoidin A and Eriodictyol

Solomon Habtemariam1 , Ermias Dagne2
  • 1Medway School of Science, The University of Greenwich, Chatham Maritime, Kent, U. K.
  • 2Department of Chemistry, Addis Ababa University, Addis Ababa, Ethiopia
Further Information

Publication History

received August 28, 2009 revised –

accepted October 21, 2009

Publication Date:
25 November 2009 (online)

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Abstract

Sigmoidin A (SGN) is a prenylated flavanone derivative of eriodictyol (ERD) with reported moderate antioxidant, antimicrobial and anti-inflammatory activity. Since ERD and other structurally similar antioxidant phenolic compounds have been shown to induce prooxidative macromolecular damage and cytotoxicity in cancer cells, the comparative in vitro effects of these structural analogues on cancer cell viability and Cu(II)-dependent DNA damage were studied. In the presence of Cu(II) ions, both SGN and ERD (7.4–236 µM) caused comparable concentration-dependent pBR322 plasmid DNA strand scission. The DNA damage induced by SGN and ERD could be abolished by ROS scavengers, glutathione (GSH) and catalase as well as EDTA and a specific Cu(I) chelator neocuproine. Both ERD and SGN readily reduce Cu(II) to Cu(I) suggesting a prooxidative mechanism of DNA damage. In a cell free system, ERD and SGN did also show comparable radical scavenging activity. SGN was, however, by an order of magnitude more cytotoxic to cancer cells than ERD and this effect was significantly attenuated by GSH suggesting a prooxidative mechanism of cell death. A depletion of intracellular GSH level by SGN in cancer cells is also demonstrated.

Key words

sigmoidin A - eriodictyol - prooxidant - DNA damage - cytotoxicity - Erythrina abyssinica - Fabaceae

References

  • 1 Ramos S. Effects of dietary flavonoids on apoptotic pathways related to cancer chemoprevention.  J Nutr Biochem. 2007;  18 427-442
    CrossrefPubMedGoogle Scholar
  • 2 Chen Y H, Chang F R, Lin Y J, Hsieh P W, Wu M J, Wu Y C. Identification of antioxidants from rhizome of Davallia solida.  Food Chem. 2008;  107 684-691
    CrossrefPubMedGoogle Scholar
  • 3 Narváez-Mastache J M, Novillo F, Delgado G. Antioxidant aryl-prenylcoumarin, flavan-3-ols and flavonoids from Eysenhardtia subcoriacea.  Phytochemistry. 2008;  69 451-456
    CrossrefPubMedGoogle Scholar
  • 4 Tsimogiannis D I, Oreopoulou V. Free radical scavenging and antioxidant activity of 5,7,3′,4′-hydroxy-substituted flavonoids.  Innov Food Sci Emerging Technol. 2004;  5 523-528
    CrossrefPubMedGoogle Scholar
  • 5 Tsimogiannis D I, Oreopoulou V. The contribution of flavonoid C-ring on the DPPH free radical scavenging efficiency. A kinetic approach for the 3′,4′-hydroxy substituted members.  Innov Food Sci Emerging Technol. 2006;  7 140-146
    CrossrefPubMedGoogle Scholar
  • 6 Melidou M, Riganakos K, Galaris D. Protection against nuclear DNA damage offered by flavonoids in cells exposed to hydrogen peroxide: the role of iron chelation.  Free Radic Biol Med. 2005;  39 1591-1600
    CrossrefPubMedGoogle Scholar
  • 7 Matsuo M, Sasaki N, Saga K, Kaneko T. Cytotoxicity of flavonoids toward cultured normal human cells.  Biol Pharm Bull. 2005;  28 253-259
    CrossrefPubMedGoogle Scholar
  • 8 Ogata S, Miyake Y, Yamamoto K, Okumura K, Taguchi H. Apoptosis induced by the flavonoid from lemon fruit (Citrus limon BURM. f.) and its metabolites in HL-60 cells.  Biosci Biotechnol Biochem. 2000;  64 1075-1078
    CrossrefPubMedGoogle Scholar
  • 9 Fomum Z T, Ayafor J F, Mbafor J T. Erythrina studies: Part 1. Novel antibacterial flavanones from Erythina sigmoidea.  Tetrahedron Lett. 1983;  24 4127-4130
    CrossrefPubMedGoogle Scholar
  • 10 Yenesew A, Induli M, Derese S, Midiwo J O, Heydenreich M, Peter M G, Akala H, Wangui J, Liyala P, Waters N C. Anti-plasmodial flavonoids from the stem bark of Erythrina abyssinica.  Phytochemistry. 2004;  65 3029-3032
    CrossrefPubMedGoogle Scholar
  • 11 Njamen D, Mbafor J T, Fomum Z T, Kamanyi A, Mbanya J C, Recio M, Giner R M, Máñez S, Ríos J L. Anti-inflammatory activities of two flavanones, sigmoidin A and sigmoidin B, from Erythrina sigmoidea.  Planta Med. 2004;  70 104-107
    Article in Thieme ConnectPubMedGoogle Scholar
  • 12 Galati G, Sabzevari O, Wilson J X, O'Brien P J. Prooxidant activity and cellular effects of the phenoxyl radicals of dietary flavonoids and other polyphenolics.  Toxicology. 2002;  177 91-104
    CrossrefPubMedGoogle Scholar
  • 13 Ichimaru M, Moriyasu M, Nishiyama Y, Kato A. Structural elucidation of new flavanones isolated from Erythrina abyssinica.  J Nat Prod. 1996;  59 1113-1116
    CrossrefPubMedGoogle Scholar
  • 14 Cui L, Ndinteh D T, Na M, Thuong P T, Silike-Muruumu J, Njamen D, Mbafor J T, Fomum Z T, Ahn J S, Oh W K. Isoprenylated fravonoids from the stembark of Erythrina abyssinica.  J Nat Prod. 2007;  70 1039-1042
    CrossrefPubMedGoogle Scholar
  • 15 Habtemariam S. Antioxidant activity of knipholone anthrone.  Food Chem. 2007;  102 1042-1047
    CrossrefPubMedGoogle Scholar
  • 16 Habtemariam S, Jackson C. Antioxidant and cytoprotective activity of leaves of Peltiphyllum peltatum (Torr.) Engl.  Food Chem. 2007;  105 498-503
    CrossrefPubMedGoogle Scholar
  • 17 Habtemariam S. Activity-guided isolation and identification of free radical-scavenging components from ethanolic extract of boneset (leaves of Eupatorium perfoliatum).  Nat Prod Commun. 2008;  3 1317-1320
    PubMedGoogle Scholar
  • 18 Habtemariam S, Dagne E. Prooxidant action of knipholone anthrone: copper dependent reactive oxygen species generation and DNA damage.  Food Chem Toxicol. 2009;  47 1490-1494
    CrossrefPubMedGoogle Scholar
  • 19 Ito M, Murakami K, Yoshino M. Antioxidant action of eugenol compounds: role of metal ion in the inhibition of lipid peroxidation.  Food Chem Toxicol. 2005;  43 461-466
    PubMedGoogle Scholar
  • 20 Jos A, Cameán M, Pflugmacher S, Segner H. The antioxidant glutathione in the fish cell lines EPC and BCF-2: response to model pro-oxidants as measured by three different fluorescent dyes.  Toxicol In Vitro. 2009;  23 546-553
    CrossrefPubMedGoogle Scholar
  • 21 Rahman A, Fazel F, Greensill J, Ainley K, Parish Y C, Hadi S M. Strand scission in DNA induced by dietary flavonoids: role of Cu(I) and oxygen free radicals and biological consequences of scission.  Mol Cell Pharmacol. 1992;  111 3-9
    PubMedGoogle Scholar
  • 22 Sandur S K, Ichikawa H, Pande M K, Kunnumakkara A B, Sung B, Sethi G, Aggarwal B B. Role of pro-oxidants and antioxidants in the anti-inflammatory and apoptotic effects of curcumin (diferuloylmethane).  Free Radic Biol Med. 2007;  43 568-580
    CrossrefPubMedGoogle Scholar
  • 23 Seifried H E, Anderson D E, Fisher E I, Milner J A. A review of the interaction among dietary antioxidants and reactive oxygen species.  J Nutr Biochem. 2007;  18 567-579
    CrossrefPubMedGoogle Scholar
  • 24 Habtemariam S. Activity-guided isolation and identification of antioxidant components from ethanolic extract of Peltiphyllum peltatum (Torr.) Engl.  Nat Prod Commun. 2008;  3 1321-1324
    PubMedGoogle Scholar
  • 25 Habtemariam S. Hamamelitannin from Hamamelis virginiana inhibits the tumour necrosis factor-α (TNF)-induced endothelial cell death in vitro.  Toxicon. 2002;  40 83-88
    CrossrefPubMedGoogle Scholar
  • 26 Habtemariam S. Flavonoids as inhibitors or enhancers of the cytotoxicity of tumor necrosis factor-alpha in L-929 tumor cells.  J Nat Prod. 1997;  60 775-778
    CrossrefPubMedGoogle Scholar
  • 27 Habtemariam S. Modulation of tumour necrosis factor-α-induced cytotoxicity by polyphenols.  Phytother Res. 1997;  11 277-280
    CrossrefPubMedGoogle Scholar
  • 28 Bhat A S, Azmi S M, Hadi S M. Prooxidant DNA breakage induced by caffeic acid in human peripheral lymphocytes: involvement of endogenous copper and a putative mechanism for anticancer properties.  Toxicol Appl Pharmacol. 2007;  218 249-255
    CrossrefPubMedGoogle Scholar
  • 29 Hadi S M, Bhat S H, Azmi A S, Hanif S, Shamim U, Ullah M F. Oxidative breakage of cellular DNA by plant polyphenols: a putative mechanism for anticancer properties.  Sem Cancer Biol. 2007;  17 370-376
    PubMedGoogle Scholar
  • 30 Song J, Shin S, Ross G. Oxidative stress induced by ascorbate causes neuronal damage in an in vitro system.  Brain Res. 2001;  895 66-72
    CrossrefPubMedGoogle Scholar
  • 31 Park S W, Lee S M. Antioxidant and prooxidant properties of ascorbic acid on hepatic dysfunction induced by cold ischemia/reperfusion.  Eur J Pharmacol. 2008;  580 401-406
    CrossrefPubMedGoogle Scholar
  • 32 Casciari J, Riordan N, Schmidt T, Meng X, Jackson J, Riordan H. Cytotoxicity of ascorbate, lipoic acid, and other antioxidants in hollow fibre in vitro tumours.  Br J Cancer. 2001;  84 1544-1550
    CrossrefPubMedGoogle Scholar
  • 33 Chen Q, Espey M G, Krishna M C, Mitchell J B, Corpe C P, Buettner G R, Shacter E, Levini M. Pharmacologic ascorbic acid concentrations selectively kill cancer cells: action as a pro-drug to deliver hydrogen peroxide to tissues.  Proc Natl Acad Sci USA. 2005;  102 13604-13609
    CrossrefPubMedGoogle Scholar
  • 34 Solovieva M E, Soloviev V V, Akatov V S. Vitamin B12b increases the cytotoxicity of short-time exposure to ascorbic acid, inducing oxidative burst and iron-dependent DNA damage.  Eur J Pharmacol. 2007;  566 206-214
    CrossrefPubMedGoogle Scholar
  • 35 Kagawa T F, Geierstanger B H, Wang A H, Ho P S. Covalent modification of guanine bases in double-stranded DNA: the 1: 2-AZ-DNA structure of dC(cacacg) in the presence of CuCl2.  J Biol Chem. 1994;  266 20175-20184
    PubMedGoogle Scholar
  • 36 Zheng L F, Wei Q Y, Cai Y J, Fang J G, Zhou B, Yang L, Liu Z L. DNA damage induced by resveratrol and its synthetic analogues in the presence of Cu (II) ions: mechanism and structure-activity relationship.  Free Radic Biol Med. 2006;  41 1807-1816
    CrossrefPubMedGoogle Scholar
  • 37 Wätjen W, Weber N, Lou Y J, Wang Z Q, Chovolou Y, Kampkötter A, Kahl R, Proksch P. Prenylation enhances cytotoxicity of apigenin and liquiritigenin in rat H4IIE hepatoma and C6 glioma cells.  Food Chem Toxicol. 2007;  45 119-124
    PubMedGoogle Scholar
  • 38 Galati G, Moridani M Y, Chan T S, O'Brien P J. Peroxidative metabolism of apigenin and naringenin versus luteolin and quercetin: glutathione oxidation and conjugation.  Free Radic Biol Med. 2001;  30 370-382
    CrossrefPubMedGoogle Scholar

Dr Solomon Habtemariam

Pharmacognosy Research Laboratories
Medway School of Science
University of Greenwich

Chatham Maritime

Kent ME4 4TB

U. K.

Phone: + 44 20 83 31 83 02

Fax: + 44 20 83 31 98 05

Email: s.habtemariam@gre.ac.uk

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