PloS one, 2011-06, Vol.6 (6), p.e20858
2011
Details
- Autor(en) / Beteiligte
- Titel
- Role and mechanism of arsenic in regulating angiogenesis
- Ist Teil von
- PloS one, 2011-06, Vol.6 (6), p.e20858
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2011
- Link zum Volltext
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Arsenic is a wide spread carcinogen associated with several kinds of cancers including skin, lung, bladder, and liver cancers. Lung is one of the major targets of arsenic exposure. Angiogenesis is the pivotal process during carcinogenesis and chronic pulmonary diseases, but the role and mechanism of arsenic in regulating angiogenesis remain to be elucidated. In this study we show that short time exposure of arsenic induces angiogenesis in both human immortalized lung epithelial cells BEAS-2B and adenocarcinoma cells A549. To study the molecular mechanism of arsenic-inducing angiogenesis, we find that arsenic induces reactive oxygen species (ROS) generation, which activates AKT and ERK1/2 signaling pathways and increases the expression of hypoxia-inducible factor 1 (HIF-1) and vascular endothelial growth factor (VEGF). Inhibition of ROS production suppresses angiogenesis by decreasing AKT and ERK activation and HIF-1 expression. Inhibition of ROS, AKT and ERK1/2 signaling pathways is sufficient to attenuate arsenic-inducing angiogenesis. HIF-1 and VEGF are downstream effectors of AKT and ERK1/2 that are required for arsenic-inducing angiogenesis. These results shed light on the mechanism of arsenic in regulating angiogenesis, and are helpful to develop mechanism-based intervention to prevent arsenic-induced carcinogenesis and angiogenesis in the future.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1932-6203eISSN: 1932-6203DOI: 10.1371/journal.pone.0020858Titel-ID: cdi_plos_journals_1304903302
- Format
- –
- Schlagworte
- Adenocarcinoma, AKT protein, Angiogenesis, Arsenic, Arsenic - toxicity, B cells, Biology, Bladder, Carcinogenesis, Carcinogens, Cell Line, Tumor, Chronic obstructive pulmonary disease, DNA methylation, Enzyme Activation - drug effects, Epithelial cells, Epithelial Cells - cytology, Epithelial Cells - drug effects, Epithelial Cells - metabolism, Exposure, Extracellular signal-regulated kinase, Gene Expression Regulation - drug effects, Humans, Hypoxia, Hypoxia-inducible factor 1, Hypoxia-Inducible Factor 1 - metabolism, Hypoxia-inducible factors, Inhibition, Kinases, Liver, Liver cancer, Lung cancer, Lung diseases, Lung Neoplasms - blood supply, Lung Neoplasms - chemically induced, Lung Neoplasms - prevention & control, Medicine, Mitogen-Activated Protein Kinase 1 - metabolism, Mitogen-Activated Protein Kinase 3 - metabolism, Neovascularization, Pathologic - chemically induced, Neovascularization, Pathologic - genetics, Neovascularization, Pathologic - metabolism, Oxygen, Pathways, Proto-Oncogene Proteins c-akt - metabolism, Reactive oxygen species, Reactive Oxygen Species - metabolism, Respiratory tract diseases, Signal transduction, Signal Transduction - drug effects, Signaling, Skin, Time Factors, Urinary bladder, Vascular endothelial growth factor, Vascular Endothelial Growth Factor A - genetics