Growth inhibition induced by antiprogestins XXXX , @entity54272 , and @entity52392 in @entity43 cells involves inhibition of @entity15308 .

@entity43 @entity588 @entity9846 @entity5438 @entity54272 @entity876 @entity15308 @entity52392 @entity13525 @entity9190 @entity230 @entity3927 @entity994
Antiprogestins have been largely utilized in reproductive medicine, yet their repositioning for oncologic use is rapidly emerging. In this study we investigated the molecular mediators of the @entity43 activity of the structurally related antiprogestins @entity3927 , @entity54272 and @entity52392 . We studied the responses of wt @entity876 OV2008 and @entity876 null SK-OV-3 cells to varying doses of @entity3927 , @entity54272 and @entity52392 . The @entity230 inhibited the growth of both cell lines with a potency of @entity3927 > @entity54272 > @entity52392 , and were cytostatic at lower doses but lethal at higher concentrations. Antiprogestin-induced lethality associated with morphological features of apoptosis, hypodiploid DNA content, DNA fragmentation, and cleavage of executer caspase substrate @entity9190 . Cell death ensued despite @entity3927 caused transient up-regulation of anti-apoptotic @entity588 , @entity54272 induced transient up-regulation of inhibitor of apoptosis @entity9846 , and @entity52392 up-regulated both @entity9846 and @entity588 . The antiprogestins induced accumulation of Cdk inhibitors @entity994 ( @entity994 ) and @entity5438 ( @entity13525 ) and increased association of @entity994 ( @entity994 ) and @entity5438 ( @entity13525 ) with @entity15308 . They also promoted nuclear localization of @entity994 ( @entity994 ) and @entity5438 ( @entity13525 ), reduced the nuclear abundances of @entity15308 and cyclin E, and blocked the activity of @entity15308 in both nucleus and cytoplasm. The cytotoxic potency of the antiprogestins correlated with the magnitude of the inhibition of @entity15308 activity, ranging from G1 cell cycle arrest towards cell death. Our results suggest that, as a consequence of their cytostatic and lethal effects, antiprogestin steroids of well-known contraceptive properties emerge as attractive new agents to be repositioned for @entity43 therapeutics.
