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. 2002 May 15;364(Pt 1):121–128. doi: 10.1042/bj3640121

Plant-derived phenolic compounds prevent the DNA single-strand breakage and cytotoxicity induced by tert-butylhydroperoxide via an iron-chelating mechanism.

Piero Sestili 1, Giuseppe Diamantini 1, Annalida Bedini 1, Liana Cerioni 1, Ilaria Tommasini 1, Giorgio Tarzia 1, Orazio Cantoni 1
PMCID: PMC1222553  PMID: 11988084

Abstract

The protective effects of selected members from a series of caffeic acid esters and flavonoids were tested in various toxicity paradigms using U937 cells, previously shown to be sensitive to either iron chelators or bona fide radical scavengers or to both classes of compounds. It was found that all the protective polyphenols were active at very low concentrations and that their effects were observed only under those conditions in which iron chelators also afforded protection. Consistently, active polyphenolic compounds, unlike the inactive ones, effectively chelated iron in an in vitro system. It follows that, at least under the experimental conditions utilized in the present study, the most prominent activity of these polyphenolic compounds resides in their ability to chelate iron. Further studies revealed that the protective effects afforded by the caffeic acid esters and flavonoids were largely mediated by the catechol moiety and that the relative biological potency of these compounds was a direct function of their lipophilicity.

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Selected References

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  1. Afanas'ev I. B., Dorozhko A. I., Brodskii A. V., Kostyuk V. A., Potapovitch A. I. Chelating and free radical scavenging mechanisms of inhibitory action of rutin and quercetin in lipid peroxidation. Biochem Pharmacol. 1989 Jun 1;38(11):1763–1769. doi: 10.1016/0006-2952(89)90410-3. [DOI] [PubMed] [Google Scholar]
  2. Aherne S. A., O'Brien N. M. Mechanism of protection by the flavonoids, quercetin and rutin, against tert-butylhydroperoxide- and menadione-induced DNA single strand breaks in Caco-2 cells. Free Radic Biol Med. 2000 Sep 15;29(6):507–514. doi: 10.1016/s0891-5849(00)00360-9. [DOI] [PubMed] [Google Scholar]
  3. Bors W., Michel C., Stettmaier K. Structure-activity relationships governing antioxidant capacities of plant polyphenols. Methods Enzymol. 2001;335:166–180. doi: 10.1016/s0076-6879(01)35241-2. [DOI] [PubMed] [Google Scholar]
  4. Brambilla L., Sestili P., Guidarelli A., Palomba L., Cantoni O. Electron transport-mediated wasteful consumption of NADH promotes the lethal response of U937 cells to tert-butylhydroperoxide. J Pharmacol Exp Ther. 1998 Mar;284(3):1112–1121. [PubMed] [Google Scholar]
  5. Brown J. E., Khodr H., Hider R. C., Rice-Evans C. A. Structural dependence of flavonoid interactions with Cu2+ ions: implications for their antioxidant properties. Biochem J. 1998 Mar 15;330(Pt 3):1173–1178. doi: 10.1042/bj3301173. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cao G., Sofic E., Prior R. L. Antioxidant and prooxidant behavior of flavonoids: structure-activity relationships. Free Radic Biol Med. 1997;22(5):749–760. doi: 10.1016/s0891-5849(96)00351-6. [DOI] [PubMed] [Google Scholar]
  7. Coleman J. B., Gilfor D., Farber J. L. Dissociation of the accumulation of single-strand breaks in DNA from the killing of cultured hepatocytes by an oxidative stress. Mol Pharmacol. 1989 Jul;36(1):193–200. [PubMed] [Google Scholar]
  8. Guidarelli A., Sestili P., Cossarizza A., Franceschi C., Cattabeni F., Cantoni O. Evidence for dissimilar mechanisms of enhancement of inorganic and organic hydroperoxide cytotoxicity by L-histidine. J Pharmacol Exp Ther. 1995 Dec;275(3):1575–1582. [PubMed] [Google Scholar]
  9. Hanasaki Y., Ogawa S., Fukui S. The correlation between active oxygens scavenging and antioxidative effects of flavonoids. Free Radic Biol Med. 1994 Jun;16(6):845–850. doi: 10.1016/0891-5849(94)90202-x. [DOI] [PubMed] [Google Scholar]
  10. Hashimoto T., Tori M., Asakawa Y., Wollenweber E. Synthesis of two allergenic constituents of propolis and poplar bud excretion. Z Naturforsch C. 1988 May-Jun;43(5-6):470–472. doi: 10.1515/znc-1988-5-625. [DOI] [PubMed] [Google Scholar]
  11. Havsteen B. Flavonoids, a class of natural products of high pharmacological potency. Biochem Pharmacol. 1983 Apr 1;32(7):1141–1148. doi: 10.1016/0006-2952(83)90262-9. [DOI] [PubMed] [Google Scholar]
  12. Iwahashi H., Ishii T., Sugata R., Kido R. The effects of caffeic acid and its related catechols on hydroxyl radical formation by 3-hydroxyanthranilic acid, ferric chloride, and hydrogen peroxide. Arch Biochem Biophys. 1990 Jan;276(1):242–247. doi: 10.1016/0003-9861(90)90033-u. [DOI] [PubMed] [Google Scholar]
  13. Laranjinha J., Vieira O., Madeira V., Almeida L. Two related phenolic antioxidants with opposite effects on vitamin E content in low density lipoproteins oxidized by ferrylmyoglobin: consumption vs regeneration. Arch Biochem Biophys. 1995 Nov 10;323(2):373–381. doi: 10.1006/abbi.1995.0057. [DOI] [PubMed] [Google Scholar]
  14. Laranjinha J., Vierira O., Almeida L., Madeira V. Inhibition of metmyoglobin/H2O2-dependent low density lipoprotein lipid peroxidation by naturally occurring phenolic acids. Biochem Pharmacol. 1996 Feb 23;51(4):395–402. doi: 10.1016/0006-2952(95)02171-x. [DOI] [PubMed] [Google Scholar]
  15. Latour I., Demoulin J. B., Buc-Calderon P. Oxidative DNA damage by t-butyl hydroperoxide causes DNA single strand breaks which is not linked to cell lysis. A mechanistic study in freshly isolated rat hepatocytes. FEBS Lett. 1995 Oct 16;373(3):299–302. doi: 10.1016/0014-5793(95)01065-m. [DOI] [PubMed] [Google Scholar]
  16. Lodovici M., Guglielmi F., Meoni M., Dolara P. Effect of natural phenolic acids on DNA oxidation in vitro. Food Chem Toxicol. 2001 Dec;39(12):1205–1210. doi: 10.1016/s0278-6915(01)00067-9. [DOI] [PubMed] [Google Scholar]
  17. Nakayama T., Yamada M., Osawa T., Kawakishi S. Suppression of active oxygen-induced cytotoxicity by flavonoids. Biochem Pharmacol. 1993 Jan 7;45(1):265–267. doi: 10.1016/0006-2952(93)90402-i. [DOI] [PubMed] [Google Scholar]
  18. Nardini M., D'Aquino M., Tomassi G., Gentili V., Di Felice M., Scaccini C. Inhibition of human low-density lipoprotein oxidation by caffeic acid and other hydroxycinnamic acid derivatives. Free Radic Biol Med. 1995 Nov;19(5):541–552. doi: 10.1016/0891-5849(95)00052-y. [DOI] [PubMed] [Google Scholar]
  19. Nardini M., Natella F., Gentili V., Di Felice M., Scaccini C. Effect of caffeic acid dietary supplementation on the antioxidant defense system in rat: an in vivo study. Arch Biochem Biophys. 1997 Jun 1;342(1):157–160. doi: 10.1006/abbi.1997.9977. [DOI] [PubMed] [Google Scholar]
  20. Ogasawara H., Fujitani T., Drzewiecki G., Middleton E., Jr The role of hydrogen peroxide in basophil histamine release and the effect of selected flavonoids. J Allergy Clin Immunol. 1986 Aug;78(2):321–328. doi: 10.1016/s0091-6749(86)80083-5. [DOI] [PubMed] [Google Scholar]
  21. Rao C. V., Desai D., Kaul B., Amin S., Reddy B. S. Effect of caffeic acid esters on carcinogen-induced mutagenicity and human colon adenocarcinoma cell growth. Chem Biol Interact. 1992 Nov 16;84(3):277–290. doi: 10.1016/0009-2797(92)90129-9. [DOI] [PubMed] [Google Scholar]
  22. Rao C. V., Desai D., Simi B., Kulkarni N., Amin S., Reddy B. S. Inhibitory effect of caffeic acid esters on azoxymethane-induced biochemical changes and aberrant crypt foci formation in rat colon. Cancer Res. 1993 Sep 15;53(18):4182–4188. [PubMed] [Google Scholar]
  23. Rice-Evans C. A., Miller N. J., Bolwell P. G., Bramley P. M., Pridham J. B. The relative antioxidant activities of plant-derived polyphenolic flavonoids. Free Radic Res. 1995 Apr;22(4):375–383. doi: 10.3109/10715769509145649. [DOI] [PubMed] [Google Scholar]
  24. Sestili P., Guidarelli A., Dachà M., Cantoni O. Quercetin prevents DNA single strand breakage and cytotoxicity caused by tert-butylhydroperoxide: free radical scavenging versus iron chelating mechanism. Free Radic Biol Med. 1998 Jul 15;25(2):196–200. doi: 10.1016/s0891-5849(98)00040-9. [DOI] [PubMed] [Google Scholar]
  25. Skaper S. D., Fabris M., Ferrari V., Dalle Carbonare M., Leon A. Quercetin protects cutaneous tissue-associated cell types including sensory neurons from oxidative stress induced by glutathione depletion: cooperative effects of ascorbic acid. Free Radic Biol Med. 1997;22(4):669–678. doi: 10.1016/s0891-5849(96)00383-8. [DOI] [PubMed] [Google Scholar]
  26. Spencer J. P., Schroeter H., Kuhnle G., Srai S. K., Tyrrell R. M., Hahn U., Rice-Evans C. Epicatechin and its in vivo metabolite, 3'-O-methyl epicatechin, protect human fibroblasts from oxidative-stress-induced cell death involving caspase-3 activation. Biochem J. 2001 Mar 15;354(Pt 3):493–500. doi: 10.1042/0264-6021:3540493. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Sud'ina G. F., Mirzoeva O. K., Pushkareva M. A., Korshunova G. A., Sumbatyan N. V., Varfolomeev S. D. Caffeic acid phenethyl ester as a lipoxygenase inhibitor with antioxidant properties. FEBS Lett. 1993 Aug 23;329(1-2):21–24. doi: 10.1016/0014-5793(93)80184-v. [DOI] [PubMed] [Google Scholar]
  28. Ueda T., Ueda T., Armstrong D. Preventive effect of natural and synthetic antioxidants on lipid peroxidation in the mammalian eye. Ophthalmic Res. 1996;28(3):184–192. doi: 10.1159/000267901. [DOI] [PubMed] [Google Scholar]
  29. Wang H., Joseph J. A. Structure-activity relationships of quercetin in antagonizing hydrogen peroxide-induced calcium dysregulation in PC12 cells. Free Radic Biol Med. 1999 Sep;27(5-6):683–694. doi: 10.1016/s0891-5849(99)00119-7. [DOI] [PubMed] [Google Scholar]

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