The BH3-mimetic gossypol and noncytotoxic doses of @entity1092 induce apoptosis by suppressing @entity7596 / XXXX / @entity16389 signaling.

@entity1 @entity137 @entity3262 @entity5 @entity19 @entity1092 @entity16626 @entity584 @entity12 @entity9190 @entity15415 @entity7596 @entity320 @entity16389
UNASSIGNED: Previously we reported that @entity1092 ( @entity3262 ) acts in synergy with GOS to enhance cell death in @entity1 DU145 cells. However, the underlying mechanism remains elusive. In this study, we observed that such synergistic @entity137 of GOS and @entity3262 could be extended to @entity1 A375, HeLa, and PC-3 @entity5 cells. GOS and @entity3262 co-treatment induced robust apoptosis as evidenced by @entity15415 /-3 activation, @entity9190 cleavage, and nuclear fragmentation. GOS and @entity3262 also markedly decreased @entity7596 protein expression. Owing to the reduction of @entity7596 , @entity584 signaling was suppressed, leading to dephosphorylation of @entity16389 . Consequently, @entity16389 was activated and the expression of its target genes, including pro-apoptotic @entity12 and Bim, was upregulated. Supporting this, @entity16389 knockdown attenuated @entity12 and Bim upregulation and apoptosis induction in GOS+ @entity3262 -treated cells. Furthermore, blocking proteasome activity by @entity16626 prevented the downregulation of @entity7596 , dephosphorylation of @entity584 and @entity16389 , and induction of apoptosis in cells co-treated with GOS and @entity3262 . In @entity19 model, GOS and @entity3262 combination significantly inhibited the growth of A375 @entity320 xenografts. Our findings indicate that GOS and @entity3262 co-treatment induces apoptosis in @entity1 @entity5 cells by suppressing the @entity7596 / @entity584 / @entity16389 pathway.
