Chloroquine as a hyperthermia potentiator.
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 degrees C with 0.005 mM CQ, 0.01 mM CQ, 0.05 mM CQ, or 0.1 mM CQ and colony formation evaluated at 7 days. CQ was cytotoxic at 37 or 41 degrees C in a dose-dependent fashion. A significant increase in cytotoxicity was seen with 0.5 and 0.1 mM CQ at 41 degrees C compared to 37 degrees C (P less than 0.01). The influence of treatment time on CQ cytotoxicity was examined by treating cells with 0.05 mM CQ at 37 or 41 degrees C for 30-min intervals from 30 to 180 min. Increasing length of exposure to CQ increased cytotoxicity at both 37 and 41 degrees C. For each interval studied treatment at 41 degrees C significantly decreased colony formation compared to treatment at 37 degrees C (P less than 0.01). Complete cell kill was achieved after 180 min of 41 degrees C treatment compared to 80% cell kill at 37 degrees C. We conclude that in this model CQ is an effective potentiator of hyperthermia.
Morrow
M
M
Department of Surgery, SUNY-Health Science Center, Brooklyn.
Hager
C
C
Berger
D
D
Djordjevic
B
B
D002470:Cell Survival; D002738:Chloroquine / Q000627:therapeutic use*; D006979:Hyperthermia, Induced; D008545:Melanoma / Q000473:pathology / Q000628:therapy*; D013696:Temperature; D013997:Time Factors; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay
D002738:Chloroquine