Nanosecond pulsed electric fields (nsPEFs) impact and enhanced Photofrin II(®) delivery in photodynamic reaction in cancer and normal cells.

BACKGROUND: Nanosecond pulsed electric field (nsPEF) treatment is a new anti-cancer strategy with ultrashort pulse duration and high intensity of electric fields. The application of nsPEFs affects all intra- and extracellular membranes and independently initiates the process of apoptosis within cancer cells, leading the tumor to slowly auto-destruct without the use of toxic drugs.

METHODS: This study involves cells of gastric adenocarcinoma (EPG85-257P and EPG85-257RDB), metastatic melanoma (Me45), epidermal cancer (A431), normal keratinocytes (HaCaT), and macrophages (P388/D1). The influence of nanosecond pulses on the cellular structure and cellular proliferation was evaluated. The effect of nsPEF was determined by MTT and clonogenic assays and the efficiency was monitored by following the propidium iodide and Photofrin II(®) uptake using FACS analysis. The cell membranes state was visualized with DHCC marker.

RESULTS: nsPEFs (up to 60kV/cm) induced significant decrease of cellular viability in all cancer cells except the A431 cell line. Photodynamic reactions combined with nsPEFs induced the highest decrease of cellular viability in both gastric cell lines and skin derived cancer cells. Normal (HaCaT and P388/D1) cells were in contrary not significantly affected. Propidium iodide and Photofrin II(®) uptake, used as markers of membrane permeabilization, were the most efficient in gastric cells. Finally, the most disturbed morphology was observed in the latter.

CONCLUSIONS: This is the first attempt of combining nsPEF with photodynamic reaction using Ph II(®) for selective destruction of cancer cells. The results indicate the potential of nsPEF for inducing cytotoxicity mainly in adenocarcinoma cells, while combined with Photofrin II(®) and irradiation.