Detection and cytotoxicity of cisplatin-induced superoxide anion in monolayer cultures of a human ovarian cancer cell line

Autor: Toshiko Tanaka, Mariko Naito, Hisamitsu Tamai, Masahiro Tateishi, Hidetaka Masuda
Rok vydání: 2001
Předmět:
Zdroj: Cancer Chemotherapy and Pharmacology. 47:155-160
ISSN: 1432-0843
0344-5704
DOI: 10.1007/s002800000198
Popis: Superoxide anions (O2-) generated by cisplatin [cis-diamminedichloroplatinum (II), DDP] were determined by measuring the chemiluminescence from the luminescence probe, 2-methyl-6-[p-methoxyphenyl]-3,7-dihydroimidazo[1,2-a]pyrazin-3-one (methyl Cypridina luciferin analog, MCLA), in monolayer cultures of a human ovarian cancer cell line (A2780) in physiological saline at pH 7.0. In a time-course study, chemiluminescence of MCLA (C-MCLA) showed a peak level at 10 min and a background level at 60 min after the addition of DDP. The intensity of C-MCLA increased with increasing concentrations of DDP or MCLA in a limited concentration range, and was significantly correlated (r = 0.960) with the number of A2780 cells. DDP-induced C-MCLA was completely inhibited by the addition of the O2- scavenger, superoxide dismutase (SOD). However, SOD did not decrease DDP cytotoxicity in terms of clonogenic cell survival. These findings suggest that DDP generates extracellular O2-, probably by interaction with the cellular membrane in A2780 cells, and O2- does not lead to cellular damage.
Databáze: OpenAIRE
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