Ouabain sensitizes tumor cells but not normal cells to radiation.

Ouabain is a cardiac glycoside that blocks the sodium, potassium-pump (Na,K-Pump). When A549 human lung adenocarcinoma cells were treated with 10(-6) M ouabain for 4 hr starting 1 hr before irradiation, they were sensitized (enhancement ratio at 1% survival 1.46 +/- .07, N = 5). Ouabain affected radiation repair because it decreased the shoulder of the cell survival curve and it sensitized cells when added after radiation. CCL-210 normal human lung fibroblasts were not radiosensitized by ouabain concentrations from 10(-8) M to 10(-5) M. These results suggest that it may be possible to exploit differences in the Na,K-pumps of normal cells and tumor cells to improve the therapeutic index of radiation.