Binding of the cytotoxic and antitumor triterpenes, cucurbitacins, to glucocorticoid receptors of HeLa cells.
1. 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.
D000970:Antineoplastic Agents / Q000378:metabolism*; D001667:Binding, Competitive; D002474:Cell-Free System; D054728:Cucurbitacins; D006367:HeLa Cells / Q000378:metabolism; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D007700:Kinetics; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D011987:Receptors, Steroid / Q000378:metabolism*; D013696:Temperature; D014315:Triterpenes / Q000378:metabolism*
D000970:Antineoplastic Agents; D011965:Receptors, Glucocorticoid; D011987:Receptors, Steroid; D014315:Triterpenes; D054728:Cucurbitacins; D006854:Hydrocortisone