Hyperthermic sensitization by hematoporphyrin on glioma cells

Abstract

This study investigated: (1) the effect of Hp as a hyperthermic sensitizer on glioma cells; and (2) the possible mechanism of hyperthermic sensitization by Hp using an exogenous scavenger specific to a particular reactive oxygen species. Hp at nontoxic doses at 37°C significantly enhanced thermal cell damage at 41.5°C and above in a dose-dependent manner. Thermal cell damage enhancement by HP was effectively suppressed by the addition of β-carotene, a singlet oxygen scavenger, or SOD, a superoxide scavenger, but not by the addition of mannitol or catalase. These results support the following hypothesis: The generation of super-oxide is increased in cells treated with Hp in combination with hyperthermia. Thermal cell damage enhancement by Hp is probably mediated by singlet oxygen generated via superoxide in an alternative pathway different from that of photo-sensitization. Hp has potential as a hyperthermic sensitizer because of the following advantages: (1) its dose-dependent enhancement of thermal cell damage; and (2) the lack of toxicity at physiological temperature at doses of Hp required for hyperthermic sensitization of tumour cells.

Key Words:

• Hyperthermia
• hematoporphyrin
• hyperthermic sensitizer
• reactive oxygen species
• malignant glioma in vitro