Reduction of phenoxyl radicals of the antitumour agent etoposide (VP-16) by glutathione and protein sulfhydryls in human leukaemia cells: Implications for cytotoxicity

Toxicology in Vitro : an International Journal Published in Association with BIBRA
J C YalowichV E Kagan

Abstract

Phenoxyl radicals are inevitable intermediates in the oxidative enzymatic metabolism of a phenolic antitumour drug, etoposide (VP-16), by peroxidases, cytochrome P-450, prostaglandin synthetase and tyrosinase, as well as in its interactions with oxygen and peroxyl radicals. It has been shown that one-electron reduction of the VP-16 phenoxyl radical by ascorbate and thiols prevents/delays its oxidative metabolism by tyrosinase both in model systems and in cell homogenates. To elucidate the role of endogenous thiols in the reduction of VP-16 phenoxyl radicals, K562 human leukaemia cells grown in Dulbecco's modified Eagle's medium which does not contain vitamin C (ascorbate) were used, thus excluding the ascorbate-dependent reduction of VP-16 phenoxyl radicals. VP-16 phenoxyl radicals were reduced by endogenous reductants in K562 cell homogenates, intracellular thiols mainly being responsible. Depletion of endogenous thiols by mersalyl acid resulted in almost complete inhibition of the ability of cell homogenates to reduce VP-16 phenoxyl radicals. Three systems were used to evaluate the contribution of thiol-dependent reduction of VP-16 phenoxyl radicals: (1) K562 cell homogenates depleted or supplemented with glutathione (GSH) in...Continue Reading

References

Oct 19, 1976·Biochemistry·K W KohnC A Friedman
Jan 1, 1978·International Review of Cytology·N S Kosower, E M Kosower
Dec 14, 1976·Biochemistry·J D Loike, S B Horwitz
Jan 1, 1992·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·D R MansJ Lankelma
Feb 1, 1991·Proceedings of the National Academy of Sciences of the United States of America·K Z GuytonT W Kensler
Jan 1, 1990·Free Radical Research Communications·N Usui, B K Sinha
Jan 1, 1991·Cancer·M L Slevin
Jan 1, 1990·Methods in Enzymology·K D Asmus
Nov 14, 1990·Biochimica Et Biophysica Acta·B K SinhaH M Eliot
Dec 7, 1988·Journal of the National Cancer Institute·J M van MaanenH M Pinedo
Feb 26, 1986·Biochemical and Biophysical Research Communications·N HaimB K Sinha
Mar 1, 1983·Environmental Health Perspectives·B KettererD J Meyer
Nov 15, 1983·Biochemical Pharmacology·B K SinhaB Kalyanaraman
Sep 1, 1993·Chemical Research in Toxicology·A H Corbett, N Osheroff
Aug 15, 1993·Archives of Biochemistry and Biophysics·F LinA W Girotti
Jan 1, 1993·Free Radical Biology & Medicine·G R Buettner, B A Jurkiewicz
Apr 1, 1993·The Biochemical Journal·L S Chubatsu, R Meneghini
Mar 1, 1993·Free Radical Biology & Medicine·M Sato, I Bremner
May 1, 1959·Archives of Biochemistry and Biophysics·G L ELLMAN

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Citations

Feb 3, 1999·Annals of the New York Academy of Sciences·V E Kagan, Y Y Tyurina
Nov 18, 2009·BMC Cancer·Emilio RojasMahara Valverde
Feb 23, 2008·Free Radical Biology & Medicine·Sarah L CuddihyChristine C Winterbourn
Sep 15, 2007·Free Radical Biology & Medicine·Kimberley A O'HaraBrian B Hasinoff

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