The binding of cucurbitacins to glucocorticoid receptors in HeLa cell-free systems and in intact cells was studied by competition with [3H]cortisol. Cucurbitacins were found to diminish the [3H]cortisol binding. 2. The difference in binding affinity at two temperatures suggest that cucurbitacins are metabolized under physiological conditions. 3. A linear correlation was observed between logarithms of relative binding affinities and of cytotoxic activities of cucurbitacins. Hence, the cucurbitacin binding to glucocorticoid receptors seems to be a necessary step for cytotoxic action of these compounds. 4. Cucurbitacin I was found to form cytoplasmic and nuclear salt-extractable complexes with glucocorticoid receptors of intact HeLa cells at 37 degrees C. Unlike cortisol, cucurbitacin I did not produce salt-resistant nuclear complexes.
