Toxicity of anticancer agents mediated by electroporation in vitro.
Electroporation is a physical event that temporarily reduces cell membrane barrier properties. Diminished membrane barrier properties are achieved by exposing cells to pulsed electric fields. When a cell has been treated with electric fields it is possible for extracellular agents to gain access to the cell interior. This process has been used in vivo to increase the uptake of chemotherapeutic agents by tumor cells which results in dramatically higher response rates than when drug is used alone. This type of treatment is called electrochemotherapy (ECT); bleomycin is most often used as the drug for this type of treatment. It was hypothesized that electroporation could be used to augment the cytotoxicity of other anticancer agents. Therefore, this study was performed in order to screen 44 different combinations of drug and cell type in vitro to identify drugs that may have higher cytotoxicity when combined with electroporation. Results from seven cell types indicate that the IC50 of bleomycin can be reduced by a factor of 100-5000 when electroporation is used to facilitate internalization. The IC50 values of cisplatin and carboplatin could be reduced by factors ranging from 3 to 13 in six different cell lines as a result of electroporation. These IC50 reductions in multiple cell lines suggest that cisplatin and carboplatin may be effective in vivo as part of ECT treatment.
Jaroszeski
M J
MJ
Department of Surgery, University of South Florida, Tampa 33612-4799, USA. mjarosze@com1.med.usf.edu
Dang
V
V
Pottinger
C
C
Hickey
J
J
Gilbert
R
R
Heller
R
R
D000970:Antineoplastic Agents / Q000494:pharmacology*; D001761:Bleomycin / Q000494:pharmacology; D016190:Carboplatin / Q000494:pharmacology; D002463:Cell Membrane Permeability; D002945:Cisplatin / Q000494:pharmacology; D018274:Electroporation; D005472:Fluorouracil / Q000494:pharmacology; D006801:Humans; D017239:Paclitaxel / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000970:Antineoplastic Agents; D001761:Bleomycin; D016190:Carboplatin; D017239:Paclitaxel; D002945:Cisplatin; D005472:Fluorouracil