| Abstract: | Possible targets to account for the qtotoxic activity of the a-methylene containing sesquiterpenes elephantopin and vernoleph, and an a-methylene-lactone steroidal derivative, 3-methoxy-16-methylene-17-oxo-17a-D homoestra-1,3,5,(10)-triene, have been studied. The compounds reduced surface and intracellular thiol levels in HeLa S3 ceb, caused an inhibition of Na+/K+-ATPase and an inhibition of the incorporation of [3H]thymidine into macromolecules. In addition, the steroidal compound, but not the sesquiterpene elephantopin, released lysosomal enzymes and caused marked changes in the structural integrity of the cells. Observed effects of α-methylene lactones on cellular respiration and [3H]thymidine uptake were not a consequence of alkylation. The results support the concept of the cell membrane and in particular Na+/K+-ATPase as a target for sesquiterpene lactone alkylation. |
