Doxorubicin Assisted by Microsecond Electroporation Promotes Irreparable Morphological Alternations in Sensitive and Resistant Human Breast Adenocarcinoma Cells

Abstract

Electroporation increases the transmembrane transport of molecules. The combination of electric pulses with cytostatic compounds is beneficial for cancer treatment. Doxorubicin (DOX) is a commonly used chemotherapeutic anticancer drug. Its fluorescence properties enable the investigation of drug distribution and metabolism. In this study, doxorubicin was enhanced by electroporation to eliminate cancer cells more effectively. The influence of electroporation on the drug uptake was evaluated in two cell lines: MCF-7/WT and MCF-7/DOX. The intracellular localization of doxorubicin and its impact on the intracellular structure organization were examined under a confocal microscope. Cellular effects were examined with the 3(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test that estimates the rate of metabolism in viable cells. The ultrastructure (TEM) of tumor cells subjected to the electric field was analyzed. An enhanced doxorubicin efficacy was observed in MCF-7/DOX cells after combination with electroporation. The response of the resistant cell line was revealed to be more sensitive to electric pulses. Electroporation-based methods may be attractive for cancer treatment in human breast adenocarcinoma, especially with acquired resistance. Electroporation enables a reduction of the effective dose of the drugs and the exposure time in this type of cancer, diminishing side effects of the systemic therapy.

Keywords

• electroporation
• electrochemotherapy
• breast cancer
• electropermeabilization
• doxorubicin
• MCF−7/WT