Doxorubicin increases intracellular hydrogen peroxide in PC3 prostate cancer cells.
We studied the effect of doxorubicin on the production of hydrogen peroxide by PC3 human prostate cancer cells, using a sensitive assay based on aminotriazole-mediated inhibition of catalase. PC3 cells exposed to increasing concentrations of doxorubicin had an increase in intracellular hydrogen peroxide that was concentration-dependent up to 1 microM doxorubicin. The apparent hydrogen peroxide concentration in the PC3 cells was 13 +/- 4 pM under basal steady-state conditions and increased to 51 +/- 13 pM after exposure to 1 microM doxorubicin for 30 min. The level of hydrogen peroxide in the medium as measured by Amplex Red did not increase as a result of doxorubicin treatment. PC3 cells overexpressing catalase were no more resistant to doxorubicin cytotoxicity as compared to non-transduced wild-type cells; therefore, the exact role of hydrogen peroxide in anthracycline cytotoxicity remains unproven. This study demonstrates that a specific oxidative event associated with the exposure of PC3 human prostate cancer cells to anthracyclines results in an increase in intracellular hydrogen peroxide.
Wagner
Brett A
BA
Department of Medicine, The University of Iowa Carver College of Medicine and Holden Comprehensive Cancer Center, Iowa City, IA 52242, USA.
Evig
Crystal B
CB
Reszka
Krzysztof J
KJ
Buettner
Garry R
GR
Burns
C Patrick
CP
D000640:Amitrole / Q000494:pharmacology; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D002374:Catalase / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005456:Fluorescent Dyes; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism*; D007424:Intracellular Fluid / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D018384:Oxidative Stress; D011471:Prostatic Neoplasms / Q000473:pathology; D017382:Reactive Oxygen Species; D014161:Transduction, Genetic; D014407:Tumor Cells, Cultured / Q000187:drug effects*
D000903:Antibiotics, Antineoplastic; D004791:Enzyme Inhibitors; D005456:Fluorescent Dyes; D017382:Reactive Oxygen Species; D004317:Doxorubicin; D006861:Hydrogen Peroxide; D002374:Catalase; D000640:Amitrole