Correlation between mammalian cell cytotoxicity of flavonoids and the redox potential of phenoxyl radical/phenol couple
Treść / Zawartość
Flavonoids exhibit prooxidant cytotoxicity in mammalian cells due to the formation of free radicals and oxidation products possessing quinone or quinomethide structure. However, it is unclear how the cytotoxicity of flavonoids depends on the ease of their single-electron oxidation in aqueous medium, i.e., the redox potential of the phenoxyl radical/phenol couple. We verified the previously calculated redox potentials for several flavonoids according to their rates of reduction of cytochrome c and ferricyanide, and proposed experimentally-based values of redox potentials for myricetin, fisetin, morin, kaempferol, galangin, and naringenin. We found that the cytotoxicity of flavonoids (n=10) in bovine leukemia virus-transformed lamb kidney fibroblasts (line FLK) and murine hepatoma (line MH-22a) increases with a decrease in their redox potential of the phenoxyl radical/phenol couple and an increase in their lipophilicity. Their cytotoxicity was decreased by antioxidants and inhibitors of cytochromes P-450, α-naphthoflavone and isoniazide, and increased by an inhibitor of catechol-O-methyltransferase, 3,5-dinitrocatechol. It shows that although the prooxidant action of flavonoids may be the main factor in their cytotoxicity, the hydroxylation and oxidative demethylation by cytochromes P-450 and O-methylation by catechol-O-methyltransferase can significantly modulate the cytotoxicity of the parent compounds.
- Awad HM, Boersma MG, Boeren S, Van der Woude H, Van Zanden J, van Bladeren PJ, Vervoort J, Rietjens IM (2002) Identification of o-quinone/quinone methide metabolites of quercetin in a cellular in vitro system. FEBS Lett 520: 30-34.
- Bandele OJ, Clawson SJ, Osheroff N (2008) Dietary polyphenols as topoisomerase II DNA-poisons: B ring and C ring substituents determine the mechanism of enzyme-mediated cleavage enhancement. Chem Res Toxicol 21: 1253-1260.
- Boersma MG, Vervoort J, Szymusiak H, Lemanska K, Tyrakowska B, Čėnas N, Segura-Aguilar J, Rietjens IM (2000) Regioselectivity and reversibility of the glutathione conjugation of quercetin quinone methide. Chem Res Toxicol 13: 185-191.
- Bolton JL, Trush MA, Penning TM, Dryhurst G, Monks TJ (2000) Role of quinones in Toxicology. Chem Res Toxicol 13: 135-160.
- Čėnas N, Nemeikaitė-Čėnienė A, Šarlauskas J, Anusevičius Ž, Nivinskas H, Misevičienė L, Marozienė A (2009) Mechanisms of the mammalian cell cytotoxicity of explosives. In Ecotoxicology of explosives. Sunahara GI, Lotufo G, Kuperman RG, Hawari J, eds, pp 211-226. CRC Press, Boca Raton, London, New York.
- Connors KA (1990) Chemical kinetics: the study of reaction rates in solution. VCH Publishers Inc., New York, Weinheim, Cambridge, 1990.
- Duarte Silva I, Rodrigues AS, Gaspar J, Laires A, Rueff J (1997) Metabolism of galangin by rat cytochromes P450: relevance to the genotoxicity of galangin. Mutat Res 393: 247-257.
- Galati G, Chan T, Wu B, O'Brien PJ (1999) Glutathione-dependent generation of reactive oxygen species by the peroxidase-catalyzed redox cycling of flavonoids. Chem Res Toxicol 12: 521-525.
- Galati G, Sabzevari O, Wilson JX, O'Brien PJ (2002) Prooxidant activity and cellular effects of the phenoxyl radicals of dietary flavonoids and other polyphenolics. Toxicology 177: 91-104.
- Gamet-Payrastre LS, Manenti S, Gratacap MP, Tulliez J, Chap H, Payrastre B (1999) Flavonoids and the inhibition of PKC and PI 3-kinase. Gen Pharmacol 32: 279-286.
- Grellier P, Nemeikaitė-Čėnienė A, Šarlauskas J, Čėnas N (2008) Role of single-electron oxidation potential and lipophilicity in the antiplasmodial in vitro activity of polyphenols: comparison to mammalian cells. Z Naturforsch C 63: 445-450.
- Hodek P, Trefil P, Stiborova M (2002) Flavonoids-potent and versatile biologically active compounds interactiong with cytochromes P450. Chem Biol Interact 139: 1-21.
- Hou DX, Kumamoto T (2010) Flavonoids as protein kinase inhibitors for cancer chemoprevention: direct binding and molecular modeling. Antioxid Redox Signal 13: 691-719.
- Hynes MJ, Coinceanainn MO (2002) Investigation of the release of iron from ferritin by naturally occurring antioxidants. J Inorg Biochem 90: 18-21.
- Inayat-Hussain SH, Winski SL, Ross D (2001) Differential involvement of caspases in hydroquinone-induced apoptosis in human leukemic HL-60 and Jurkat cells. Toxicol Appl Pharmacol 175: 95-103.
- Jorgensen LV, Skibsted LH (1998) Flavonoid deactivation of ferrylmyoglobin in relation to ease of oxidation as determined by cyclic voltammetry. Free Radic Res 28: 335-351.
- Jovanovic SV, Steenken S, Simic MG, Hara Y (1998) Antioxidant properties of flavonoids: reduction potentials and electron transfer reactions of flavonoid radicals. In: Flavonoids in health and disease. Rice-Evans CA, Packer L, eds, pp 137-161. Marcel Dekker Inc, New York, Basel, Hong Kong.
- Lautala P, Ulmanen I, Taskinen J (2002) Molecular mechanisms controlling the rate and specificity of catechol-O-methylation by human soluble catechol-O-methyltransferase. Mol Pharmacol 59: 393-402.
- Lee WJ, Shim JY, Zhu BT (2005) Mechanisms for the inhibition of DNA methyltransferases by thea catechins and bioflavonoids. Mol Pharmacol 68: 1018-1030.
- Lee MH, Han DW, Hyon SH, Park JC (2011) Apoptosis of human fibrosarcoma HT-1080 cells by epigallocatechin-3-O-gallate via induction of p53 and caspases as well as suppression of Bcl-2 and phosphorylated nuclear factor-κB. Apoptosis 16: 75-85.
- Lin WZ, Navaratnam S, Yao SD, Lin NY (1998) Antioxidative properties of hydroxycinnamic acid derivatives and a phenylpropanoid glycoside. A pulse radiolysis study. Radiat Phys Chem 53: 425-430.
- Lu J, Papp LV, Rodriguez-Nieto S, Zhivotovsky B, Holmgren A (2006) Inhibition of mammalian thioredoxin reductase by some flavonoids: implications for myricetin and quercetin anticancer activity. Cancer Res 66: 4410-4417.
- Marcus RA, Sutin N (1985) Electron transfers in chemistry and biology. Biochim Biophys Acta 811: 265-322.
- Metodiewa D, Jaiswal AK, Čėnas N, Dičkancaitė E, Segura-Aguilar J (1999) Quercetin may act as a cytotoxic prooxidant after its metabolic activation to semiquinone and quinoidal product. Free Rad Biol Med 26: 107-116.
- Miyoshi N, Naniwa K, Yamada T, Osawa T, Nakamura Y (2007) Dietary flavonoid apigenin is a potential inducer of intracellular oxidative stress: the role in the interruptive apoptotic signal. Arch Biochem Biophys 466: 274-282.
- Moini H, Arroyo A, Vaya J, Packer L (1999) Bioflavonoid effects on the mitochondrial respiratory electron transport chain and cytochrome c redox state. Redox Rep 4: 35-41.
- Moridani MY, Cheon SS, Khan S, O'Brien PJ (2002a) Metabolic activation of 4-hydroxyanisole by isolated rat hepatocytes. Drug Metab Dispos 30: 1063-1069.
- Moridani MY, Scobie H, O'Brien PJ (2002b) Metabolism of caffeic acid by isolated rat hepatocytes and subcellular fractions. Toxicol Lett 133: 141-151.
- Moridani MY, Siraki A, O'Brien PJ (2003) Quantitative structure toxicity relationships for phenols in isolated rat hepatocytes. Chem-Biol Interact 145: 213-223.
- Morin D, Barthelemy S, Zini R, Labidalle S, Tillement JP (2001) Curcumin induces the mitochondrial permeability transition pore by membrane protein thiol oxidation. FEBS Lett 495: 131-136.
- Morita K, Arimochi H, Ohnishi Y (2003) In vitro cytotoxicity of 4-methylcatechol in murine tumor cells: induction of apoptotic cell death by extracellular pro-oxidant action. J Pharmacol Exp Ther 306: 317-323.
- Mouria M, Gukovskaya AS, Jung Y, Buechler P, Hines OJ, Reber HA, Pandol SJ (2002) Food-derived polyphenols inhibit pancreatic cancer growth through mitochondrial cytochrome c release and apoptosis. Int J Cancer 98: 761-769.
- Nemeikaitė-Čėnienė A, Imbrasaitė A, Sergedienė E, Čėnas N (2005) Quantitative structure-activity relationships in prooxidant cytotoxicity of polyphenols: role of potential of phenoxyl radical/phenol redox couple. Arch Biochem Biophys 441: 182-190.
- Nielsen SE, Breinholt V, Justesen U, Cornett C, Dragsted LO (1998) In vitro biotransformation of flavonoids by rat liver microsomes. Xenobiotica 28: 389-401.
- O'Brien PJ (1991) Molecular mechanisms of quinone cytotoxicity. Chem-Biol Interact 80: 1-41.
- Oikawa S, Furukawa A, Asada H, Hirakawa K, Kawanishi S (2003) Catechins induce oxidative damage to cellular and isolated DNA through the generation of reactive oxygen species. Free Radic Res 37: 881-8980.
- Öllinger K, Brunmark A (1991) Effect of hydroxy substituent position on 1,4-naphthoquinone toxicity to rat hepatocytes. J Biol Chem 266: 21496-21503.
- Rich PR (1982) Electron and proton transfers in chemical and biochemical quinone systems. Faraday Discuss Chem Soc 74: 349-364.
- Rich PR, Bendall DS (1980) The kinetics and thermodynamics of the reduction of cytochrome c by substituted p-benzoquinols in solution. Biochim Biophys Acta 592: 506-518.
- Robaszkiewicz A, Balcerczyk A, Bartosz G (2007) Antioxidative and prooxidative effects of quercetin on A549 cells. Cell Biol Int 31: 1245-1250.
- Salvi M, Brunati AM, Clari G, Toninello A (2002) Interaction of genistein with the mitochondrial electron transport chain results in the opening of the membrane transition pore. Biochim Biophys Acta 1556: 187-156.
- Sergedienė E, Jönsson K, Szymusiak H, Tyrakowska B, Rietjens IM, Čėnas N (1999) Prooxidant toxicity of polyphenolic antioxidants to HL-60 cells: description of quantitative structure-activity relationships. FEBS Lett 462: 392-396.
- Sharma V, Joseph C, Ghosh S, Agarwal A, Mishra MK, Sen E (2007) Kaempferol induces apoptosis in glioblastoma cells through oxidative stress. Mol Cancer Ther 6: 2544-2553.
- Shen SC, Ko CH, Tseng SW, Tsai SH, Chen YC (2004) Structurally related antitumor effects of flavanones in vitro and in vivo: involvement of caspase 3 activation, p21 gene expression, and reactive oxygen species production. Toxicol Appl Pharmacol 197: 84-95.
- Terland O, Almås B, Flatmark T, Andersson KK, Sorlie M (2006) One-electron oxidation of catecholamines generates free radicals with an in vitro toxicity correlating with their lifetime. Free Rad Biol Med 41: 1266-1271.
- Uchimiya M, Gorb L, Isayev O, Qasim MM, Leszczynski J (2010) One-electron standard reduction potentials of nitroaromatic and cyclic nitramine explosives. Environ Pollut 158: 3048-3053.
- Wardman P (1989) Reduction potentials of one-electron couples involving free radicals in aqueous solutions. J Phys Chem Ref Data 18: 1637-1755.
- Webb MR, Ebeler SE (2004) Comparative analysis of topoisomerase IB inhibition and DNA intercalation by flavonoids and similar compounds: structural determinantes of activity. Biochem J 384: 527-541.
- Yoshino M, Murakami K (1998) Interaction of iron with polyphenolic compounds: application to antioxidant characterization. Anal Biochem 257: 40-44.
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