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.
Department of Physiology, Medical School, Chonbuk National University, JeonJu, Republic of Korea.
Hwa Jin
HJ
Moon
Woo Hyun
WH
Park
D017209:Apoptosis / Q000187:drug effects*; D002083:Butylated Hydroxyanisole / Q000494:pharmacology*; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D005978:Glutathione / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D017382:Reactive Oxygen Species / Q000378:metabolism
D061945:Caspase Inhibitors; D015853:Cysteine Proteinase Inhibitors; D017382:Reactive Oxygen Species; D002083:Butylated Hydroxyanisole; D020169:Caspases; D005978:Glutathione