Journal article
Autophagy is a cell self-protective mechanism against arsenic-induced cell transformation
Toxicological sciences, Vol.130(2), pp.298-308
12/2012
DOI: 10.1093/toxsci/kfs240
PMID: 22869613
Abstract
Subchronic exposure to arsenic increases the incidence of human cancers such as skin, lung, colon, and rectal cancer. The mechanism for arsenic-induced tumorigenesis is still not clear. It is generally believed that DNA damage and genomic instability, generated by arsenic-promoted oxidative stress, account largely for this process. The major sources of reactive oxygen species (ROS) are arsenic-damaged mitochondria. Autophagy is a catabolic process functioning in turnover of long-lived proteins and dysfunctional organelles such as mitochondria. Defects of autophagy under stress conditions promote genomic instability and increase the risk of tumorigenesis. In the present study using a human bronchial epithelial cell line, BEAS-2B cells, we investigated the role of autophagy in arsenic-induced cell transformation, an important step in arsenic tumorigenesis. Our results show that subchronic arsenic exposure induces BEAS-2B cell transformation accompanied with increased ROS generation and autophagy activation. However, the patterns for ROS and autophagy alteration are different. Arsenic exposure generated a prolonged and steady increase of ROS levels, whereas the activation of autophagy, after an initial boost by arsenic administration, decreases in response to subchronic arsenic exposure, although the activity is still higher than a nontreated control. Further stimulation of autophagy increases mitochondria turnover and decreases ROS generation and arsenic-induced cell transformation. Contrarily, inhibition of autophagy activity decreases mitochondria turnover and enhances arsenic-induced ROS generation and cell transformation. In addition, the mammalian target of rapamycin signaling pathway is involved in arsenic-mediated autophagy activation. Our results suggest that autophagy is a cell self-protective mechanism against arsenic-induced cell transformation.
Details
- Title: Subtitle
- Autophagy is a cell self-protective mechanism against arsenic-induced cell transformation
- Creators
- Tao Zhang - University of KentuckyYuanlin Qi - University of KentuckyMingjun Liao - University of KentuckyMei Xu - University of KentuckyKimberley A Bower - University of KentuckyJacqueline A Frank - University of KentuckyHan-Ming ShenJia Luo - University of KentuckyXianglin Shi - University of KentuckyGang Chen - University of Kentucky
- Resource Type
- Journal article
- Publication Details
- Toxicological sciences, Vol.130(2), pp.298-308
- DOI
- 10.1093/toxsci/kfs240
- PMID
- 22869613
- ISSN
- 1096-6080
- eISSN
- 1096-0929
- Language
- English
- Date published
- 12/2012
- Academic Unit
- Pathology
- Record Identifier
- 9984201113802771
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