| Cycloheximide(CHX) is a typical protein synthesis inhibitor ofeukaryotes and can inhibit apoptosis induced by various stimuli, so it has beenwidely used in studies of the molecular mechanisms of apoptosis. The factsthat CHX can selectively induce apoptosis and restrain the multidrugresistance in a certain extent lead us to try in as anti-tumor medicine. In this study, we firstly described the relationships of etoposide andCHX on the apoptosis effect of U937. CHX could prevent etoposide-inducedapoptosis by totally blocking de novo protein synthesis. Ectoposide stronglypromoted CHX-induced U937 apoptosis, but did not alter its selection of celltypes. These findings suggest that a high percentage of quick and selectiveinduction of apoptosis would be achieved if CHX and etoposide are used incombination, and may set up new theoretical bases for developing effectivedrugs with lower side effects of cancer therapy. And then, we investigated the molecular mechanisms of the apoptosiseffect of CHX on U937 enhanced by etoposide. Since CHX can block de novoprotein synthesis, etoposide may promote the apoptosis effect throughPKCδ phospharylation and cleavage. The results showed that when etoposideand CHX were both added on U937, apoptosis was improved with the level ofPKCδ phospharylation increased distinctly, which could be blocked when theselective inhibitor of PKCδ used. However, how the activated PKCδ promotesthe other cytokines to enhance the apoptosis effect of CHX on U937 remainsunclear.
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