Gallic acid-induced human pulmonary fibroblast cell death is accompanied by increases in ROS level and GSH depletion.
Gallic acid (GA), as a polyhydroxylphenolic compound, has various biological properties, including an anticancer effect. However, little is known about the toxicological effect of GA in primary normal cells. In the present study, we investigated the molecular mechanisms of GA on human pulmonary fibroblast (HPF) cell death in relation to apoptosis. HPF cell growth was dose dependently diminished with an IC(50) of approximately 400 μM of GA at 24 hours. GA-induced HPF cell death was accompanied by the loss of mitochondrial membrane potential (MMP; ΔΨ(m)). All the tested caspase inhibitors (e.g., pan-caspase, caspase-3, -8, or -9 inhibitor) did not rescue HPF cells from GA-induced cell death. GA increased reactive oxygen species (ROS) levels and glutathione (GSH)-depleted cell numbers. Caspase inhibitors partially altered ROS levels, but did not reduce GSH-depleted cell number, in GA-treated HPF cells. In conclusion, we demonstrated that GA induced the growth inhibition and death of HPF cells, which was accompanied by ROS increase and GSH depletion.
Department of Physiology, Medical School, Institute for Medical Sciences, Chonbuk National University, JeonJu, Republic of Korea.
Bo Ra
BR
You
Woo Hyun
WH
Park
D017209:Apoptosis / Q000187:drug effects*; D018929:Cell Culture Techniques; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005707:Gallic Acid / Q000633:toxicity*; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism*
D017382:Reactive Oxygen Species; D005707:Gallic Acid; D005978:Glutathione