Electroporation and alternating current cause membrane permeation of photodynamic cytotoxins yielding necrosis and apoptosis of cancer cells

In order to increase the permeability of cell membranes for low doses of cytostatic drugs, two bioelectrochemical methods have been compared: (a) electric pore formation in the plasma membranes by single electric impulses (electroporation), and (b) reordering of membrane structure by alternating currents (capacitively coupled). These treatments were applied to human leukemic K-562 cells and human lymphoma U-937 cells, yielding apoptotic and necrotic effects, determinated by flow cytometry. Additional cell death occurs after exposure to light irradiation at wavelengths lambda>600 nm, of cells which were electroporated and had incorporated actinomycin-C or daunomycin (daunorubicine). It is observed that drug uptake after an exponentially decaying electroporation pulse of the initial field strength Eo= 1.4 kV/cm and pulse time constants in the time range 0.5-3 ms is faster than during PEMF-treatment, i.e., application of an alternating current of 16 kHz, voltage U< 100 V, I = 55 mA, and exposure time 20 min. However, at the low ac. voltage of this treatment, more apoptotic and necrotic cells are produced as compared to the electroporation treatment with one exponentially decaying voltage pulse. Thus, additional photodynamic action appears to be more effective than solely drugs and electroporation as applied in clinical electrochemotherapy, and more effective than the noninvasive pulsed electromagnetic fields (PEMEs), for cancer cells in general and animals bearing tumors in particular. (C) 2010 Published by Elsevier B.V.