Chloroquine as a hyperthermia potentiator

Abstract

The antimalarial agent chloroquine (CQ) inhibits DNA and RNA polymerase and interferes with lysosomal function. We sought to determine if these properties make chloroquine effective as a hyperthermia sensitizer. B16F10 melanoma cells were treated for 180 min at 37 or 41°C with 0.005 m M CQ, 0.01 m M CQ, 0.05 m M CQ, or 0.1 m M CQ and colony formation evaluated at 7 days. CQ was cytotoxic at 37 or 41°C in a dose-dependent fashion. A significant increase in cytotoxicity was seen with 0.5 and 0.1 m M CQ at 41°C compared to 37°C ( P < 0.01). The influence of treatment time on CQ cytotoxicity was examined by treating cells with 0.05 m M CQ at 37 or 41°C for 30-min intervals from 30 to 180 min. Increasing length of exposure to CQ increased cytotoxicity at both 37 and 41°C. For each interval studied treatment at 41°C significantly decreased colony formation compared to treatment at 37°C ( P < 0.01). Complete cell kill was achieved after 180 min of 41°C treatment compared to 80% cell kill at 37°C. We conclude that in this model CQ is an effective potentiator of hyperthermia.