Carbonyl cyanide p -(trifluoromethoxy) phenylhydrazone (FCCP) as an O2− generator induces apoptosis via the depletion of intracellular GSH contents in Calu-6 cells

• Published in: Lung cancer (Amsterdam, Netherlands) Netherlands), 2009-02, Vol.63 (2), p.201-209
• Main Authors: Han, Yong Hwan, Kim, Suhn Hee, Kim, Sung Zoo, Park, Woo Hyun
• Format: Article
• Language: English
• Subjects: Adenocarcinoma - metabolism; Adenocarcinoma - pathology; Apoptosis - drug effects; Biological and medical sciences; Buthionine Sulfoximine - pharmacology; Calu-6; Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone - pharmacology; Cell Line, Tumor; Dithiothreitol - pharmacology; FCCP; Free Radical Scavengers - pharmacology; Glutathione - metabolism; GSH; Hematology, Oncology and Palliative Medicine; Humans; Lung Neoplasms - metabolism; Lung Neoplasms - pathology; Medical sciences; Mitochondria; Pneumology; Pulmonary/Respiratory; ROS; ROS scavenger; Superoxides - metabolism; Tumors; Tumors of the respiratory system and mediastinum
• ISSN: 0169-5002; 1872-8332
• DOI: 10.1016/j.lungcan.2008.05.005

Summary Carbonyl cyanide p -(trifluoromethoxy) phenylhydrazone (FCCP) is an uncoupler of mitochondrial oxidative phosphorylation in eukaryotic cells. Here, we investigated an involvement of O2− and GSH in FCCP-induced Calu-6 cell death and examined whether ROS scavengers rescue cells from FCCP-induced cell death. Levels of intracellular O2− were markedly increased depending on the concentrations (5–100 μM) of FCCP. A depletion of intracellular GSH content was also observed after exposing cells to FCCP. Stable SOD mimetics, Tempol and Tiron did not change the levels of intracellular O2− , apoptosis and the loss of mitochondrial membrane potential (Δ Ψm ). Treatment with thiol antioxidants, NAC and DTT, showed the recovery of GSH depletion and the reduction of O2− levels in FCCP-treated cells, which were accompanied by the inhibition of apoptosis. In contrast, BSO, a well-known inhibitor of GSH synthesis, aggravated GSH depletion, oxidative stress of O2− and cell death in FCCP-treated cells. Taken together, our data suggested that FCCP as an O2− generator, induces apoptosis via the depletion of intracellular GSH contents in Calu-6 cells.