Autophagy Is a Cell Self-Protective Mechanism Against Arsenic-Induced Cell Transformation
Open Access
- 5 August 2012
- journal article
- research article
- Published by Oxford University Press (OUP) in Toxicological Sciences
- Vol. 130 (2), 298-308
- https://doi.org/10.1093/toxsci/kfs240
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.Keywords
This publication has 46 references indexed in Scilit:
- The multiple roles of autophagy in cancerCarcinogenesis: Integrative Cancer Research, 2011
- Role of autophagy in suppression of inflammation and cancerCurrent Opinion in Cell Biology, 2010
- Mammalian autophagy: core molecular machinery and signaling regulationCurrent Opinion in Cell Biology, 2010
- Dual Role of 3-Methyladenine in Modulation of Autophagy via Different Temporal Patterns of Inhibition on Class I and III Phosphoinositide 3-KinaseJournal of Biological Chemistry, 2010
- Autophagy: cellular and molecular mechanismsThe Journal of Pathology, 2010
- Autophagy is a protective mechanism in normal cartilage, and its aging‐related loss is linked with cell death and osteoarthritisArthritis & Rheumatism, 2010
- Role of autophagy in cancerNature Reviews Cancer, 2007
- Ethanol promotes endoplasmic reticulum stress‐induced neuronal death: Involvement of oxidative stressJournal of Neuroscience Research, 2007
- Functional and physical interaction between Bcl-XL and a BH3-like domain in Beclin-1The EMBO Journal, 2007
- Endogenous IL-12 triggers an antiangiogenic program in melanoma cellsProceedings of the National Academy of Sciences of the United States of America, 2007