Electrochemical monitoring of anticancer compounds on the human ovarian carcinoma cell line A2780 and its adriamycin- and Cisplatin-resistant variants.
A novel electrochemical technique which detects and monitors real-time changes in cell behavior in vitro has been used to examine the effects of recognized anticancer drugs on the human ovarian carcinoma cell line A2780 and its adriamycin (A2780adr)- and cisplatin (A2780cispt)-resistant variants. These cells, adherent to gold electrodes or sensors, modify the extracellular microenvironment at the cell:sensor interface, producing an electrochemical potential that is different from that of the bulk culture medium. Confluent, adherent A2780 cells produced an electrochemical signal, measured as an open circuit potential (OCP), of approximately -100 mV compared to a cell-free value of approximately -15 mV. Exposure of A2780 cells to cisplatin (range 10(-4) to 10(-6) M), adriamycin (range 10(-5) to 10(-7) M), and vinblastine (10(-6) M) all produced positive shifts in the OCP signal relative to untreated control cells during 24 h of culture, but Taxotere (range 10(-5) to 10(-7) M) had no effect. These positive shifts in OCP signal were evident well before observations of reduced cellular adhesion and viability after 24 h, as judged in parallel cultures with a plastic substratum and by scanning electron microscopy. By contrast, the same treatments applied to the A2780adr and A2780cispt variants showed that each demonstrated different sensitivities to the same drugs applied to the parental A2780 cells. The effects of the same four anticancer drugs on ovarian carcinoma (A2780) and breast carcinoma (8701-BC) cell lines showed that the former was far more responsive to adriamycin and cisplatin. Such differences in drug sensitivities between the two cell lines were subsequently confirmed using the conventional MTT assay over 5 days. Although this electrochemical technology readily detects changes in cell adhesion and viability, the modified OCP signals recorded within a few hours of anticancer drug treatments are evident well before microscopic morphological changes become apparent. It is proposed that these early changes in OCP signals, relative to control untreated cells, reflect modifications of physiological/behavioral processes manifested at the cell surface.
Woolley
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DE
University Department of Medicine, Manchester Royal Infirmary, Oxford Road, Manchester, M13 9WL, United Kingdom. david.woolley@mri.nwest.nhs.uk
Tetlow
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Adlam
D J
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Gearey
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Eden
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RD
Ward
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Allen
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D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002448:Cell Adhesion / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000627:therapeutic use; D000077143:Docetaxel; D004317:Doxorubicin / Q000627:therapeutic use; D016903:Drug Monitoring; D019008:Drug Resistance, Neoplasm; D004563:Electrochemistry / Q000379:methods; D005260:Female; D006801:Humans; D008855:Microscopy, Electron, Scanning; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D017239:Paclitaxel / Q000031:analogs & derivatives* / Q000627:therapeutic use; D043823:Taxoids; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014747:Vinblastine / Q000627:therapeutic use
D000970:Antineoplastic Agents; D043823:Taxoids; D000077143:Docetaxel; D014747:Vinblastine; D004317:Doxorubicin; D017239:Paclitaxel; D002945:Cisplatin