Disparity in the induction of glutathione depletion, ROS formation, poly(ADP-ribose) polymerase-1 activation, and apoptosis by quinonoid derivatives of naphthalene in human cultured cells

摘要: Abstract The purpose of this study is to examine the differences in induction cytotoxic effects and poly(ADP-ribose) polymerase-1 activation human MCF-7 breast cancer cells by quinonoid derivatives naphthalene, including 1,2-naphthalenediol (NCAT), 1,4-naphthalenediol (NHQ), 1,2-naphthoquinone (1,2-NQ), 1,4-naphthoquinone (1,4-NQ). Results from response analyses indicated that all naphthalene quinonoids induced cell death at concentrations ranging 0.1 100 μM where NHQ 1,4-NQ were more efficient than NCAT 1,2-NQ death. Western blot confirmed treatment with resulted up-regulation p53 protein expression a significant shift bax/bcl2 ratio, suggesting p53-dependent apoptosis cells. Additionally, we observed increases reactive oxygen species (ROS) formation glutathione (GSH) depletion ROS GSH decreases rank order 1,4-NQ > NHQ > 1,2-NQ ≅ NCAT. Further investigation least-squares estimates overall rates elimination ( k e ) decreased 1,4-NQ > 1,2-NQ > NHQ > NCAT. Values estimated be between 0.280 h −1  ( T 1/2  = 151 min) 13.8 h  = 3.05 min). These results provide evidence para -isomeric form tend induce acute production alterations intracellular redox status cells, leading subsequent Further, NAD(P)H NAD + non-cytotoxic concentrations. reduction exposed was blocked two types polymerase (PARP) inhibitors whereas PARP did not prevent 1,4-NQ. number DNA single-strand breaks detected as measured single-cell gel electrophoresis (Comet) assay Overall, our suggest while are death, prone mediated PARP-1 through cultured