Perfluorooctane sulfonate induces apoptosis in lung cancer A549 cells through reactive oxygen species‐mediated mitochondrion‐dependent pathway

Abstract

Perfluorooctane sulfonate (PFOS) is a widespread environmental contaminant that is detected in the lung of mammals. The mechanisms underlying PFOS-induced lung cytotoxicity remain unclear. The main purpose of this study was to evaluate the cytotoxic effects of PFOS on human lung cancer A549 cells and its possible molecular mechanism. A549 cells were treated with PFOS (0, 25, 50, 100 and 200 μm) and the cellular apoptosis, mitochondrial membrane potential as well as intracellular reactive oxygen species were determined. In this study, PFOS induced a dose-dependent increase in A549 cell toxicity via an apoptosis pathway as characterized by increased percentage of sub-G1, activation of caspase-3 and -9, and increased ratio of Bax/bcl-2 mRNA expression. In addition, there was obvious oxidative stress, represented by decreased glutathione level, increased malondialdehyde level and superoxide dismutase activity. N-Acetylcysteine, as an antioxidant that is a direct reactive oxygen species scavenger, can effectively block PFOS-induced reactive oxygen species generation, mitochondrial membrane potential loss and cell apoptosis. These data indicate that PFOS induces apoptosis in A549 cells through a reactive oxygen species-mediated mitochondrial dysfunction pathway mechanism.

Chronic Exposure to Perfluorooctane Sulfonate Induces Behavior Defects and Neurotoxicity through Oxidative Damages, In Vivo and In Vitro

“…Furthermore, we observed that PFOS induced a decrease in GSH level, and an increase in MDA level and SOD in a dose-depend manner. It is consistent with another description in lung cancer A549 cells [50] . According to previous studies, the level of MDA reflects the degree of radical lipid peroxidation in cells.…”

“…In addition, PFOS-induced apoptosis was raised in a dose-dependent manner. Previous studies have also shown the PFOS-induced apoptosis in lung cancer A549 cells and cerebellar granule cells [49] , [50] . These, along with our results, indicate that apoptosis is an important factor in the cytotoxicity of PFOS.…”

Paraquat Induces Apoptosis through a Mitochondria-Dependent Pathway in RAW264.7 Cells

“…Cell apoptosis is a highly regulated process of programmed cell death that is important for modulating cell numbers ( Fiers et al ., 1999 ; Fadeel and Orrenius, 2005 ). Many intrinsic and extrinsic factors, especially caspases ( Fuchs and Steller, 2011 ; Mao et al ., 2013 ) and Bcl-2 superfamily proteins ( Martinou and Youle, 2011 ) regulate apoptosis ( Fuchs and Steller, 2011 ). PQ has been reported to induce apoptosis in some mammalian cells ( Cappelletti et al ., 1998 ; Li and Sun, 1999 ; Rio and Velez-Pardo, 2008 ).…”

“…7 ). The mitochondria, a critical intracellular organelle, plays an essential role in the regulation of apoptosis ( Green and Kroemer, 2004 ; Orrenius, 2004 ; Mao et al ., 2013 ). ROS-induced MMP depolarization is involved in apoptosis related to mitochondrial dysfunction ( Chipuk et al ., 2006 ).…”

“…ROS-induced MMP depolarization is involved in apoptosis related to mitochondrial dysfunction ( Chipuk et al ., 2006 ). MMP depolarization induces a permeability transition, allowing for the release of pro-apoptotic factors, including cytochrome c, from mitochondria into the cytosol, thereby triggering caspase-dependent or caspase-independent cytosolic signaling events ( Green and Kroemer, 2004 ; Orrenius, 2004 ; Mao et al ., 2013 ). In this study, exposure of RAW264.7 cells to PQ induced MMP depolarization.…”