Auranofin Enhances Sulforaphane-Mediated Apoptosis in Hepatocellular Carcinoma Hep3B Cells through Inactivation of the PI3K/Akt Signaling Pathway.

摘要: The thioredoxin (Trx) system plays critical roles in regulating intracellular redox levels and defending organisms against oxidative stress. Recent studies indicated that Trx reductase (TrxR) was overexpressed various types of human cancer cells indicating the Trx-TrxR may be a potential target for anti-cancer drug development. This study investigated synergistic effect auranofin, TrxR-specific inhibitor, on sulforaphane-mediated apoptotic cell death using Hep3B cells. results showed sulforaphane significantly enhanced auranofin-induced apoptosis by inhibiting TrxR activity proliferation compared to either single treatment. auranofin evidenced an increased annexin-V-positive Sub-G1 induction combined treatment caused loss mitochondrial membrane (ΔΨm) upregulation Bax. In addition, proteolytic activities caspases (-3, -8, -9) degradation poly (ADP-ribose) polymerase, substrate protein activated caspase-3, were also higher Moreover, induced excessive generation reactive oxygen species (ROS). However, with N-acetyl-L-cysteine, ROS scavenger, reduced treatment-induced production apoptosis. Thereby, these deduce played pivotal role sulforaphane. Furthermore, through inhibition phosphoinositide 3-kinase (PI3K)/Akt pathway. Taken together, present demonstrated down-regulation contributed PI3K/Akt signaling