BETA-LAPACHONE ENHANCEMENT OF LIPID PEROXIDATION AND SUPEROXIDE ANION AND HYDROGEN-PEROXIDE FORMATION BY SARCOMA-180 ASCITES TUMOR-CELLS

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 O- 2 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 O- 2, (c) production of H2O2 via Superoxide dismutase reaction and generation of HO· from the reaction of O- 2 and H2O2 with subsequent stimulation of lipid peroxidation and decreased viability of the cells. © 1979.