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Aflatoxin G1-induced oxidative stress causes DNA damage and triggers apoptosis through MAPK signaling pathway in A549 cells

Author:
Shen, Haitao, Liu, Jing, Wang, Yuan, Lian, Hongguang, Wang, Juan, Xing, Lingxiao, Yan, Xia, Wang, Junling, Zhang, Xianghong
Source:
Food and chemical toxicology 2013 v.62 pp. 661-669
ISSN:
0278-6915
Subject:
DNA, DNA damage, acetylcysteine, adenocarcinoma, aflatoxin G1, antioxidants, apoptosis, carcinogenesis, caspase-3, caspase-8, cell viability, humans, mitogen-activated protein kinase, neoplasm cells, oxidative stress, pretreatment, rats, reactive oxygen species, signal transduction
Abstract:
Our previous studies showed that Aflatoxin G1 (AFG1) could induce lung adenocarcinoma, and that the cancer cells originated from alveolar type II cells (AT-II cells). Recently, we found AFG1 induced structural impairment in rat AT-II cells, which may account for an early event in lung tumorigenesis. However, the mechanism of AFG1-induced AT-II cell damage remains unclear. DNA damage and apoptosis induced by oxidative stress are well accepted causes of cell damage. Thus, we explore whether AFG1 activates the reactive oxygen species (ROS)/MAPK/apoptosis pathway to cause cell damage in human AT-II cells like the cell line (A549). We found AFG1 induced oxidative stress by increasing ROS generation and caused DNA double-strand breaks (DSBs) by up-regulating γH2AX expression. AFG1 also triggered apoptosis in A549 cells by regulating Fas/FasL, caspase-8, Bax, Bcl-2, and activating caspase-3. Pre-treatment with antioxidant n-acetyl-l-cysteine (NAC) reduced ROS generation and DNA DSBs, inhibited apoptosis, and increased cell viability in AFG1-treated cells. Furthermore, we found AFG1 activated ROS-mediated JNK and p38 pathways to induce cell apoptosis in A549 cells. In conclusion, our results indicate that AFG1 induces oxidative DNA damage and triggers apoptosis through ROS-mediated JNK and p38 signaling pathways in A549 cells, which may contribute to AFG1-induced AT-II cell damage.
Agid:
865853