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PMID: 21687637 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

Role and mechanism of arsenic in regulating angiogenesis.

PloS one ·Vol. 6 ·No. 6 ·2011-00-00 ·Pages e20858

Liu LZ, Jiang Y, Carpenter RL, Jing Y, Peiper SC, Jiang BH

Abstract

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.

MeSH Terms
Arsenic/toxicity Cell Line, Tumor Enzyme Activation/drug effects Epithelial Cells/cytology,drug effects,metabolism Gene Expression Regulation/drug effects Humans Hypoxia-Inducible Factor 1/metabolism Lung Neoplasms/blood supply,chemically induced,prevention & control Mitogen-Activated Protein Kinase 1/metabolism Mitogen-Activated Protein Kinase 3/metabolism Neovascularization, Pathologic/chemically induced,genetics,metabolism Proto-Oncogene Proteins c-akt/metabolism Reactive Oxygen Species/metabolism Signal Transduction/drug effects Time Factors Vascular Endothelial Growth Factor A/genetics
Chemicals
Hypoxia-Inducible Factor 1 Reactive Oxygen Species Vascular Endothelial Growth Factor A Proto-Oncogene Proteins c-akt Mitogen-Activated Protein Kinase 1 Mitogen-Activated Protein Kinase 3 Arsenic
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Liu Ling-Zhi
Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, Pennsylvania, United States of America.
Jiang Yue
Carpenter Richard L
Jing Yi
Peiper Stephen C
Jiang Bing-Hua
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Article Info
Journal
PloS one
Abbr.
PLoS One
ISSN
1932-6203
DOI
10.1371/journal.pone.0020858
Published
2011-00-00
Epub
2011-00-08
Pages
e20858
Language
English
Region
United States
NLM ID
101285081
PMCID
PMC3110823
Subset
IM
Grants
NHLBI NIH HHS · R01HL091456 · United States
NIEHS NIH HHS · R21 ES017237 · United States
NCI NIH HHS · R01 CA109460 · United States
NIEHS NIH HHS · R21ES017237 · United States
NHLBI NIH HHS · R01 HL091456 · United States
NCI NIH HHS · R01CA109460 · United States
External Links
PubMed source DOI: 10.1371/journal.pone.0020858 PMC Full Text View journal details
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