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2014 | 61 | 4 | 795-799
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The antioxidant quercetin protects HL-60 cells with high myeloperoxidase activity against pro-oxidative and apoptotic effects of etoposide

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The protective action of quercetin against the pro-oxidant and apoptotic effect of etoposide was investigated in HL-60 cells with a high level of myeloperoxidase (MPO) activity and in cells treated with MPO inhibitor, 4-aminobenzoic acid hydrazide (ABAH). Quercetin significantly protected MPO-rich cells against the pro-oxidative (p<0.05) and apoptotic (p<0.05) effects of etoposide. Pre-treatment with ABAH abolished this protective influence of quercetin on apoptosis induced by etoposide but actually enhanced the action effect of quercetin against etoposide-generated reactive oxygen species (ROS) level by this cytostatic drug. Thus quercetin can protect HL-60 cells against the pro-oxidative activity of etoposide regardless of MPO activity.
Physical description
  • Department of Cytobiology, Faculty of Pharmacy, Jagiellonian University, Medical College, Kraków, Poland
  • Department of Medical Diagnostics, Jagiellonian University, Medical College, Faculty of Pharmacy, Kraków, Poland
  • Bender RP, Lindsey RH, Burden DA, Osheroff N (2004) N-acetyl-p-benzoquinone imine, the toxic metabolite of acetaminophen is a topoisomerase II poison. Biochemistry 43: 3731-3739.
  • Cheng IF, Breen K (2000) On the ability of four flavonoids, baicilein, luteolin, naringenin, and quercetin, to suppress the Fenton reaction of the iron-ATP complex. Biometals 13: 77-83.
  • Choi JS, Piao YJ, Kang KW (2011) Effects of quercetin on the bioavailability of doxorubicin in rats: role of CYP3A4 and P-gp inhibition by quercetin. Arch Pharm Res 34: 607-613.
  • Fan Y, Schreiber EM, Giorgianni A, Yalowich JC, Day BW (2006) Myeloperoxidase-catalyzed metabolism of etoposide to its quinone and glutathione adduct forms in HL60 cells. Chem Res Toxicol 19: 937-943.
  • Gantchev TG, Hunting DG (1998) The ortho-quinone metabolite of the anticancer drug etoposide (VP-16) is a potent inhibitor of the topoisomerase II/DNA cleavable complex. Mol Pharmacol 53: 422-428.
  • Hu JP, Calomme M, Lasure A, De Bruyne T, Pieters L, Vlietinck A, Vanden Berghe DA (1995) Structure-activity relationship of flavonoids with superoxide scavenging ability. Biol Trace Elem Res 47: 327-331.
  • Jacob DA, Mercer SL, Osheroff N, Deweese JE (2011) Etoposide quinone is a redox-dependent topoisomerase ii poison. Biochemistry 50: 5660-5667.
  • Kagan VE, Yalowich JC, Borisenko GG, Tyurina YY, Tyurin VA, Thampatty P, Fabisiak JP (1999) Mechanism-based chemopreventive strategies against etoposide-induced acute myeloid leukemia: free radical/antioxidant approach. Mol Pharmacol 56: 494-506.
  • Kapiszewska M, Cierniak A, Elas M, Lankoff A (2007) Lifespan of etoposide-treated human neutrophils is affected by antioxidant ability of quercetin. Toxicology in Vitro 21: 1020-1030.
  • Karanjawala ZE, Murphy N, Hinton DR, Hsieh CL, Lieber MR (2002) Oxygen metabolism causes chromosome breaks and is associated with the neuronal apoptosis observed in DNA doublestrand break repair mutants. Curr Biol 12: 397-402.
  • Kobayashi K, Ratain MJ (1994) Pharmacodynamics and long-term toxicity of etoposide. Cancer Chemother Pharmacol 34: S64-S68.
  • Lovett BD, Strumberg D, Blair IA, Pang S, Burden DA, Megonigal MD, Rappaport EF, Rebbeck TR, Osheroff N, Pommier YG, Felix CA (2001) Etoposide metabolites enhance DNA topoisomerase II cleavage near leukemia-associated MLL translocation breakpoints. Biochemistry 40: 1159-1170.
  • Moon YJ, Wang X, Morris ME (2006) Dietary flavonoids: effects on xenobiotic and carcinogen metabolism. Toxicol In Vitro 20: 187-210.
  • Papież MA (2014) The effect of quercetin on oxidative DNA damage and myelosuppression induced by etoposide in bone marrow cells of rats. Acta Biochim Pol 61: 7-11.
  • Pincemail J, Deby C, Thirion A, de Bruyn-Dister M, Goutier R (1988) Human myeloperoxidase activity is inhibited in vitro by quercetin. Comparison with three related compounds. Experientia 44: 450-453.
  • Ramyaa P, Krishnaswamy R, Padma VV (2014) Quercetin modulates OTA-induced oxidative stress and redox signalling in HepG2 cells - up regulation of Nrf2 expression and down regulation of NF-κB and COX-2. Biochim Biophys Acta 1840: 681-92.
  • Sallmyr A, Fan J, Rassool FV (2008) Genomic instability in myeloid malignancies: increased reactive oxygen species (ROS), DNA double strand breaks (DSBs), and error-prone repair. Cancer Lett 270: 1-9.
  • Samuel T, Fadlalla K, Mosley L, Katkoori V, Turner T, Manne U (2012) Dual-mode interaction between quercetin and dna-damaging drugs in cancer cells. Anticancer Res 32: 61-71.
  • Slevin ML (1991) The clinical pharmacology of etoposide. Cancer 67: 319-329.
  • Spagnuolo C, Russo M, Bilotto S, Tedesco I, Laratta B, Russo GL (2012) Dietary polyphenols in cancer prevention: the example of the flavonoid quercetin in leukemia. Ann NY Acad Sci 1259: 95-103.
  • Vlasova II, Feng WH, Goff JP, Giorgianni A, Do D, Gollin SM, Lewis DW, Kagan VE, Yalowich JC (2011) Myeloperoxidase-dependent oxidation of etoposide in human myeloid progenitor CD34+cells. Mol Pharmacol 79: 479-487.
  • Whitlock JA, Greer JP, Lukens JN (1991) Epipodophyllotoxin-related leukemia. Identification of a new subset of secondary leukemia. Cancer 68: 600-604.
  • Wiczkowski W, Romaszko J, Bucinski A, Szawara-Nowak D, Honke J, Zielinski H, Piskula MK (2008) Quercetin from shallots (allium cepa l. var. aggregatum) is more bioavailable than its glucosides. J Nutr 138: 885-888.
  • Yuan Z, Long Ch, Junming T, Qihuan L, Youshun Z, Chan Z (2012) Quercetin-induced apoptosis of HL-60 cells by reducing PI3K/Akt. Mol Biol Rep 39: 7785-7793.
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