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

Abstract

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.

• Authors: H Masuda, T Tanaka, M Tateishi, M Naito, H Tamai
• Journal: Cancer chemotherapy and pharmacology (Cancer Chemother Pharmacol) Vol. 47 Issue 2 Pg. 155-60 ( 2001) ISSN: 0344-5704 [Print] Germany
• PMID: 11269742 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• Imidazoles
• Pyrazines
• Superoxides
• 2-methyl-6-(4-methoxyphenyl)-3,7-dihydroimidazo(1,2-alpha)pyrazin-3-one
• Superoxide Dismutase
• Cisplatin

Topics

• Antineoplastic Agents (pharmacology)
• Cell Survival (drug effects)
• Cisplatin (pharmacology)
• Female
• Humans
• Imidazoles
• Luminescent Measurements
• Ovarian Neoplasms (drug therapy, metabolism, pathology)
• Pyrazines
• Superoxide Dismutase (pharmacology)
• Superoxides (analysis, metabolism)
• Tumor Cells, Cultured