Heat Enhances the Anti-Cancer Effect of β-Lapachone

초록

We have previously reported that β-lapachone, originally isolated from the bark of the Lapacho tree, is a potent anti-cancer drug and that radiation synergistically enhances the anti-cancer effect of β-lapachone in vitro and in vivo. Indications are that radiation exposure increases the expression of NAD(P)H:quinone oxidoreductase, NQO1, which then activates β-lapachone. In the present study, we investigated the enhancement of β-lapachone cytotoxicity by hyperthermia. An incubation of cells with 5 μM β-lapachone for 4 h at 37°C reduced the survival of clonogenic cells to 20% while heating the cells at 41°C for 1 h exerted no effect on the cell survival. The combined effect of heating and β-lapachone was studied by heating the cells at 41-43°C for 1 h either during the first or last 1 h of a 4 h exposure to 5 μM β-lapachone. Heating at 41°C for 1 h during the first 1 h of a 4 h exposure to 5 μM β-lapachone reduced the clonogenic cell survival to 6% as compared with 20% after β-lapachone treatment alone. Thermosensitization was further increased as the heating temperature was raised to 42 or 43°C. Heating the cells during the last 1h of a 4 h β-lapachone exposure was less effective than heating the cells during the first 1 h. Our results clearly indicated that the anti-cancer effect of β -lapachone can be enhanced by both radiation and hyperthermia