Electrochemical red-ox therapy of prostate cancer in nude mice

•EChT-mediated water hydrolysis generates cytotoxic acidic and alkaline ions in cells.•EChT-induced damages are not heat-mediated.•EChT triggers immediate histopathological lesions in tumors.•EChT is accompanied by a sharp decline in blood PSA.•Optimized EChT parameters for maximal damages in tumors

Minimally invasive therapies are increasingly in demand for organ-confined prostate tumors. Electrochemical therapy (EChT) is attractive, as it relies on locally-induced reduction–oxidation reactions to kill tumor cells. Its efficacy for prostate cancer was assessed in human PC-3 and LNCaP tumor xenografts growing subcutaneously in nude mice (n = 80) by applying 2 Stainless Steel vs. 4 Platinum–Iridium (Pt–Ir) electrodes to deliver current densities of 10 to 35 mA/cm2 for 30 or 60 min. The procedure was uneventful in 90% of mice. No difference in tumor vs. body temperature was observed. Changes at electrode-tumor junctions were immediate, with dryness and acidity (pH 2–3) at the anode and oedema and alkalinity (pH 10–12) at the cathode. This was accompanied by cellular alterations, found more pronounced at the cathode. Such acidic and alkaline conditions were cytotoxic in vitro and dissolved cells at pH > 10. In mice, tumor destruction was extensive by 24 h with almost undetectable blood prostate specific antigen (LNCaP model) and covered the whole tumor surface by 4 days. EChT was most efficient at 25–30 mA/cm2 for 60 min, yielding the longest recurrence-free survival and higher cure rates, especially with 4 Pt–Ir electrodes. EChT is a promising option to optimize for organ-confined prostate tumors.