Elsevier

Biochemical Pharmacology

Volume 28, Issue 6, 15 March 1979, Pages 723-728
Biochemical Pharmacology

β-lapachone enhancement of lipid peroxidation and superoxide anion and hydrogen peroxide formation by Sarcoma 180 ascites tumor cells

https://doi.org/10.1016/0006-2952(79)90348-4Get rights and content

Abstract

Addition of β-lapachone, an o-naphthoquinone endowed with antitumor properties for Sarcoma 180 cells, induced the formation of a semiquinone radical. β-Lapachone was able to stimulate Superoxide anion and hydrogen peroxide production by the mitochondrial fraction supplemented with NADH. β-Lapachone also increased O2 and H2O2 production by the microsomal fraction with NADPH as reductant. Cyanide-insensitive NADH and NADPH oxidations by the mitochondrial and microsomal fractions (quinone reductase activity) were stimulated to about the same extent by β-lapachone. Incubation of sarcoma cells with β-lapachone stimulated lipid peroxidation and resulted in a decrease in the viability of the cells. The toxicity of β-lapachone to tumor cells was reduced by incubation of the cells with the free radical scavenger, α-tocopherol. The basic mechanism of the biological action of β-lapachone in sarcoma cells seems to be: (a) reduction at the mitochondrial and microsomal membranes with generation of the semiquinone form, (b) autoxidation of the semiquinone free radical with primary production of O2, (c) production of H2O2 via Superoxide dismutase reaction and generation of HO· from the reaction of O2 and H2O2 with subsequent stimulation of lipid peroxidation and decreased viability of the cells.

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    Permanent address: Instituto de Química Biológica, Facultad de Medicina, Universidad de Buenos Aires, Paraguay 2155, Buenos Aires, Argentina.

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