Aroclor 1254 inhibits cell viability and induces apoptosis of human A549 lung cancer cells by modulating the intracellular Ca²⁺level and ROS production through the mitochondrial pathway

Abstract

To study the acute toxic effects of PCBs on airway exposure, the cell viability, apoptosis and mitochondrial functions of human lung cancer cell line A549 were measured and compared after Aroclor 1254 exposure for different time. The results showed that Aroclor 1254 could inhibit cell viability and increase cell apoptosis in a concentration- and time-dependent manner. The mitochondrial apoptosis pathway was confirmed playing an important role. ROS elevation was an early response within 1h treatment of Aroclor 1254. Then after 4 h of Aroclor 1254 exposure, the intracellular calcium level increased and mitochondrial transmembrane potential (ΔΨm) collapsed, accompanying with Cytochrome c (Cyt-c) leakage, boosting expression of Bax, Apaf-1 and miRNA155, which were involved in the mitochondrial apoptosis pathway. After 24 h of Aroclor 1254 exposure, ROS returned to normal level, but cell apoptosis rate was higher than that at 4 h with ΔΨm continued collapsing and intracellular calcium increased. In conclusion, Aroclor 1254 could suppress cell viability and induce apoptosis in A549 cells, which was associated with ROS over-production and elevated cellular Ca(2+) level, which may result in mitochondrial dysfunction, inducing expression of Bax/Cyt-c/Apaf-1 and miRNA155.

Chlorinated biphenyls effect on estrogen-related receptor expression, steroid secretion, mitochondria ultrastructure but not on mitochondrial membrane potential in Leydig cells

“…Zhong et al ( 2015 ) demonstrated that Aroclor 1254 exposure suppressed cell viability and induced apoptosis in A549 cells (lung cell line). This was associated with reactive oxygen species overproduction and an elevated cellular Ca2+ level, which all resulted in mitochondrial membrane potential dysfunction.…”

Exposure to decabromodiphenyl ether (BDE-209) produces mitochondrial dysfunction in rat liver and cell death

“…However, different mechanisms might trigger apoptotic cell death (Ouyang et al 2012), and MPT-mediated by BDE-209 in isolated rat liver mitochondria may also have occurred in HepG2 cells as evident from decreased MMP, cyt c release, and caspase 9 activation, all of which also occurred in the case of HepG2 incubation with this compound . Cyt c release is also correlated with apoptotic cell death of other persistent organic pollutants, such as PCB (Abella et al 2015;Selvakumar et al 2011;Zhong et al 2015). Although lower BDE-209 concentrations did not significantly alter cyt c levels, activation of caspase 9 was noted.…”

Divergent Effects of Dioxin- or Non-Dioxin-Like Polychlorinated Biphenyls on the Apoptosis of Primary Cell Culture from the Mouse Pituitary Gland

“…Since PCBs have been reported to increase intracellular ROS content [ 50 , 51 ], we evaluated whether PCBs-mediated changes of ROS intervene in the regulation of pituitary cells apoptosis. As shown in Fig 7A , the ROS levels did not change when cells were exposed to individual PCBs, either alone or in combination with vitamin C, a ROS production inhibitor.…”

“…Recent data suggest that ROS may have a direct role in mediating death receptor activation and the mithocondrial pathway after exposure to Aroclor 1254 [ 51 , 64 ]. In addition, chondrocytes exposed to non-dioxin-like PCBs have been reported to undergo several changes, including necrosis and apoptosis, mediated, in part by oxidative stress [ 65 ].…”