Full-text resources of PSJD and other databases are now available in the new Library of Science.
Visit https://bibliotekanauki.pl

PL EN


Preferences help
enabled [disable] Abstract
Number of results
2014 | 61 | 4 | 833-836

Article title

Cytotoxicity of anticancer aziridinyl-substituted benzoquinones in primary mice splenocytes

Content

Title variants

Languages of publication

EN

Abstracts

EN
The anticancer activity of aziridinyl-quinones is mainly attributed to their NAD(P)H:quinone oxidoreductase 1 (NQO1)-catalyzed two-electron reduction into DNA-alkylating products. However, little is known about their cytotoxicity in primary cells, which may be important in understanding their side effects. We found that the cytotoxicity of aziridinyl-unsubstituted quinones (n = 12) in mice splenocytes with a low amount of NQO1, 4 nmol × mg-1 × min-1, was caused mainly by the oxidative stress. Aziridinyl-benzoquinones (n = 6) including a novel anticancer agent RH1 were more cytotoxic than aziridinyl-unsubstituted ones with the similar redox properties, and their cytotoxicity was not decreased by an inhibitor of NQO1, dicumarol. The possible reasons for their enhanced cytotoxicity are discussed.

Year

Volume

61

Issue

4

Pages

833-836

Physical description

Dates

published
2014
received
2014-07-13
revised
2014-10-07
accepted
2014-11-12
(unknown)
2014-12-18

Contributors

  • Institute of Biochemistry of Vilnius University, Vilnius, Lithuania
  • Institute of Biochemistry of Vilnius University, Vilnius, Lithuania
  • Institute of Biochemistry of Vilnius University, Vilnius, Lithuania

References

  • Alcain FJ, Villalba JM (2007) NQO1-directed antitumour quinones. Expert Opin Ther Pat 17: 649-665.
  • Anusevičius Ž, Nivinskas H, Šarlauskas J, Sari MA, Boucher JL, Čėnas N (2013) Single-electron reduction of quinone and nitroaromatic xenobiotics by recombinant rat neuronal nitric oxide synthase. Acta Biochim Pol 60: 217-222.
  • Begleiter A (2000) Clinical applications of quinone-containing alkylating agents. Frontiers Biosci 5: e153-e171.
  • Cameron DW, Gilles RGF (1968) Photochemical formation of benzoxalizone derivatives from aminated quinones. J Chem Soc C 1461-1464.
  • Čėnas N, Anusevičius Ž, Nivinskas H, Misevičienė L, Šarlauskas J (2004) Structure-activity relationships in two-electron reduction of quinones. Methods Enzymol 382: 258-277.
  • Chou F, Khan AH, Driscoll JS (1976) Potential central nervous system antitumour agents. Aziridinylbenzoquinones. J Med Chem 19: 1302-1308.
  • Danson SJ, Johnson P, Ward TH, Dawson M, Denneny O, Dickinson G, Aarons L, Watson A, Jowle D, Cummings J, Robson L, Halbert G, Dive C, Ranson M (2011) Phase I pharmacokinetic and pharmacodynamic study of the bioreductive drug RH1. Ann Oncol 22: 1653-1660.
  • Di Francesco A, Ward TH, Butler J (2004) Diaziridinylbenzoquinones. Methods Enzymol 382: 174-193.
  • Hacker MP, Hong CB, McKee MJ, Unwin SE, Urbanek SA (1982) Toxicity of aziridinylbenzoquinone administrated intra venously to beagle dogs. Cancer Treat Rep 66: 1845-1852.
  • Hargreaves RHJ, Hartley JA, Butler J (2000) Mechanisms of action of quinone-containing alkylating agents: DNA alkylation by aziridinylquinones. Frontiers Biosci 5: e172-e180.
  • Huang CH, Kuo HS, Liu JW, Lin YL (2009) Synthesis and antitumor evaluation of novel bis-triaziquone derivatives. Molecules 14: 2306-2316.
  • Hussein D, Holt SV, Brookes KE, Klymenko T, Adamski JK, Hogg A, Estlin EJ, Ward T, Dive C (2009) Preclinical efficacy of the bioreductive alkylating agent RH1 against paediatric tumours. Br J Cancer 101: 55-63.
  • Kligerman AD, Erexson GL, Bryant MF (1988) Sister chromatid exchange induction by diaziquone in human and mouse lymphocytes following both in vivo and in vitro exposures. Cancer Res 48: 27-31.
  • Lee CS, Hartley JA, Berardini MD, Butler J, Siegel D, Ross D, Gibson NW (1992) Alteration in DNA cross-linking and sequence selectivity of a series of aziridinylbenzoquinones after enzymatic reduction by DT-diaphorase. Biochemistry 31: 3019-3025.
  • Li B, Gutierrez PL, Amstad P, Blough NV (1999) Hydroxyl radical production by mouse epidermal cell lines in the presence of quinone anti-cancer compounds. Chem Res Toxicol 12: 1042-1049.
  • Lind C, Cadenas E, Hochstein P, Ernster L (1990) DT-diaphorase: purification, properties, and function. Methods Enzymol 186: 287-301.
  • Nemeikaitė-Čėnienė A, Šarlauskas J, Anusevičius Ž, Nivinskas H, Čėnas N (2003) Cytotoxicity of RH1 and related aziridinylbenzoquinones: involvement of activation by NAD(P)H:quinone oxidoreductase (NQO1) and oxidative stress. Arch Biochem Biophys 416: 110-118.
  • Oberley LW, Buettner GR (1979) Role of superoxide dismutase in cancer: a review. Cancer Res 39: 1141-1149.
  • O'Brien PJ (1991) Molecular mechanisms of quinone cytotoxicity. Chem-Biol Interact 80: 1-41.
  • Öllinger K, Brunmark A (1991) Effect of hydroxy substituent position on 1,4-naphthoquinone toxicity to rat hepatocytes. J Biol Chem 266: 21496-21503.
  • Parkinson EI, Bair JS, Cismesia M, Hergenrother PJ (2013) Efficient NQO1 substrates are potent and selective anticancer agents. ACS Chem Biol 8: 2173-2183.
  • Petersen S, Gauss W, Urbschat E (1955) Synthese einfacher chinon-derivation mit fungiziden, bakteriostatischen oder cytostatischen eigenschaften. Angew Chem 67: 1461-1464.
  • Schallreuter KU, Wood JK, Berger J (1991) Low catalase levels in the epidermis of patients with vitiligo. J Invest Dermacol 97: 1081-1085.
  • Stack AS, Altman-Hamamdzic S, Morris PJ, London SD, London L (1999) Polychlorinated biphenyl mixtures (Aroclors) inhibit LPS-induced murine splenocyte proliferation in vitro. Toxicology 139: 137-154.
  • Tudor G, Alley M, Nelson CM, Huang R, Covell D, Gutierrez P, Sausville EA (2005) Cytotoxicity of RH1: NAD(P)H:quinone acceptor oxidoreductase (NQO1)-independent oxidative stress and apoptosis induction. Anti-Cancer Drugs 16: 381-391.
  • Ward TH, Danson S, McGown AT, Ranson M, Coe NA, Jayson GC, Hargreaves RHJ, Butler J (2005) Preclinical evaluation of the pharmacodynamic properties of 2,3-diaziridinyl-3-hydroxymethyl-6-methyl-1,4-benzoquinone. Clin Cancer Res 11: 2695-2701.
  • Wardman P (1989) Reduction potentials of one-electron couples involving their radicals in aqueous solutions. J Phys Chem Ref Data 18: 1637-1755.
  • Wardman P, Dennis MF, Everet SA, Patel KB, Stratford MR, Tracy M (1995) Radicals from one-electron reduction of nitro compounds, aromatic N-oxides and quinones: the kinetic basisfor hypoxia-selective bioreductive drugs. Biochem Soc Symp 61: 171-194.
  • Winski SL, Hargreaves RHJ, Butler J, Ross D (1998) A new screening system for NAD(P)H:quinone oxidoreductase (NQO1)-directed antitumour quinones: Identification of a new aziridinylbenzoquinone RH1, an NQO1-directed antitumour agent. Clin Cancer Res 4: 3083-3088.
  • Winski SL, Swann E, Hargreaves RHJ, Dehn DL, Butler J, Moody CJ, Ross D (2001) Relationship between NAD(P)H:quinone oxidoreductase 1 (NQO1) levels in a series of stably transfected cell lines and susceptibility to antitumor quinones. Biochem Pharmacol 61: 1509-1516.
  • Yan C, Kepa JK, Siegel D, Stratford IJ, Ross D (2008) Dissecting the role of multiple reductases in bioactivation and cytotoxicity of the antitumour agent 2,5-diaziridinyl-3-(hydroxymethyl)-6-methyl-1,4-benzoquinone (RH1). Mol Pharmacol 74: 1657-1665.

Document Type

Publication order reference

Identifiers

YADDA identifier

bwmeta1.element.bwnjournal-article-abpv61p833kz
JavaScript is turned off in your web browser. Turn it on to take full advantage of this site, then refresh the page.