Antimycin A induces death of the human pulmonary fibroblast cells via ROS increase and GSH depletion

作者：Park Woo Hyun; You Bo Ra

来源：International Journal of Oncology, 2016, 48(2): 813-820.

DOI：10.3892/ijo.2015.3276

• human pulmonary fibroblast
• anti-mycin A
• cell death
• reactive oxygen species
• glutathione

Antimycin A (AMA) inhibits the growth of various cells via stimulating oxidative stress-mediated death. However, little is known about the anti-growth effect of AMA on normal primary lung cells. Here, we investigated the effects of AMA on cell growth inhibition and death in human pulmonary fibroblast (HPF) cells in relation to reactive oxygen species (ROS) and glutathione (GSH) levels. AMA inhibited the growth of HPF cells with an IC50 of similar to 150 mu M at 24 h. AMA induced a G1 phase arrest of the cell cycle and it also triggered apoptosis accompanied by the loss of mitochondrial membrane potential (MMP; Delta Psi(m)). AMA increased ROS levels including O-2(center dot)-in HPF cells from the early time point of 25 min. It induced GSH depletion in HPF cells in a dose-dependent manner. Z-VAD (a pan-caspase inhibitor) did not significantly prevent cell death and MMP (Delta Psi(m)) loss induced by AMA. N-acetylcysteine (NAC; an antioxidant) attenuated cell growth inhibition, death and MMP (Delta Psi(m)) loss in AMA-treated HPF cells and NAC generally decreased the ROS level in these cells as well. Vitamin C enhanced cell growth inhibition, death, GSH depletion and O-2(center dot)-levels in 100 mu M AMA-treated HPF cells whereas this agent strongly attenuated these effects in 200 mu M AMA-treated cells. In conclusion, AMA inhibited the growth of HPF cells via apoptosis as well as a G1 phase arrest of the cell cycle. AMA-induced HPF cell death was related to increased ROS levels and GSH depletion.

• 出版日期2016-2