Butylated hydroxyanisole inhibits the growth of HeLa cervical cancer cells via caspase-dependent apoptosis and GSH depletion

Butylated hydroxyanisole (BHA), a synthetic antioxidant is commonly used as a preservative in food and pharmaceutical agents. Despite the assumed low toxicity of BHA, it exerts a variety of effects on tissues and cell functions. In this study, the authors investigated the effects of BHA on the growth inhibition and death of HeLa cervical cancer cells. Dose-dependent inhibition of cell growth was observed with an IC ₅₀ of approximately 150 μM BHA at 24 h. In addition, this agent-induced apoptosis, which was accompanied by the loss of mitochondrial membrane potential (ΔΨ _m) and caspase activation. Caspase-3 and -8 inhibitors markedly rescued HeLa cells from BHA-induced cell death. In addition, BHA decreased intracellular ROS levels in HeLa cells whereas it increased O ₂ ^•- levels among ROS. The number of glutathione (GSH)-depleted cells was increased in 150 μM BHA-treated cells, which was attenuated by caspase inhibitors. In conclusion, BHA inhibited the growth of HeLa cells via caspase-dependent apoptosis, which seemed to be related to increase in GSH depletion and O ₂ ^•- level.