Caspase inhibitor decreases apoptosis in pyrogallol-treated lung cancer Calu-6 cells via the prevention of GSH depletion

Pyrogallol (PG) is a polyphenol compound and is known to be an O₂^- generator. In the present study, we evaluated the anti-apoptotic effects of caspase inhibitors in relation to changes in reactive oxygen species (ROS) and glutathione (GSH) levels in PG-treated human pulmonary adenocarcinoma Calu-6 cells. Treatment with 50 μM PG inhibited the growth of Calu-6 cells ∼60% and induced apoptosis ∼17% at 24 h, accompanied by mitochondrial membrane potential loss (ΔΨm). Treatment with pan-caspase inhibitor (Z-VAD-FMK), caspase-3 inhibitor (Z-DEVD-FMK), caspase-8 inhibitor (Z-IETD-FMK) and caspase-9 inhibitor (Z-LEHD-FMK) significantly prevented apoptosis in PG-treated Calu-6 cells at 24 h. PG increased the ROS and depleted GSH contents in Calu-6 cells. Treatment with each caspase inhibitor did not significantly change the ROS and GSH levels in PG-treated Calu-6 cells at 24 h. However, Z-VAD significantly prevented GSH depletion in PG-treated Calu-6 cells at the late time phase of 72 h. Conclusively, the anti-anoptotic effect of caspase inhibitor on PG-induced Calu-6 cell death was closely related to changes in GSH content rather than ROS levels.