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.
Lawrence
T S
TS
Radiation Oncology Branch, National Cancer Institute, Bethesda, MD 20892.
D000230:Adenocarcinoma / Q000473:pathology / Q000503:physiopathology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D066298:In Vitro Techniques; D008168:Lung / Q000166:cytology / Q000502:physiology; D008175:Lung Neoplasms / Q000473:pathology / Q000503:physiopathology; D009369:Neoplasms / Q000473:pathology / Q000503:physiopathology*; D010042:Ouabain / Q000494:pharmacology*; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*
D011838:Radiation-Sensitizing Agents; D010042:Ouabain