Arsenite Induces HIF-1a and VEGF Through PI3K, Akt and Reactive Oxygen Species in DU145 Human Prostate Carcinoma Cells

Details

• Personal Author:
  Gao N ; He H ; Jiang BH ; Leonard, Stephen S. ; Shen L ; Shi X ; Zhang XG ; Zhang Z
• Description:
  Arsenite is widely distributed environmental toxicant in water, food and air. It is a known human carcinogen, which is strongly associated with human cancers originated from liver, nasal cavity, lung, skin, bladder, kidney, and prostate. In this study, we investigated whether arsenite induces expression of hypoxia-inducible factor 1 (HIF-1). HIF-1 is a heterodimeric basic helix-loop-helix transcription factor, composed of HIF-1alpha and HIF-1beta/ARNT subunits; and is involved in tumor growth and angiogenesis. Here we demonstrate that arsenite induces the expression of HIF-1alpha but not HIF-1beta subunit in DU145 human prostate carcinoma cells. Arsenite also increases the expression of VEGF through the induction of HIF-1. We also found that arsenite activates PI3K and Akt that are required for arsenite-induced expression of HIF-1alpha and VEGF. The induction of HIF-1 and VEGF by arsenite can not be inhibited by MAP kinase inhibitors. Arsenite causes production of reactive oxygen species (ROS). The major species of ROS required for the induction of HIF-1 and VEGF is H2O2. These data indicate that the arsenite-induced activation of PI3K/Akt signaling and the expression of HIF-1 and VEGF through the generation of ROS could be an important mechanism in the arsenite-induced carcinogenesis. [Description provided by NIOSH]
• Subjects:
  Antioxidants Arsenic Carcinogens Genetics Inorganic Chemicals Mutagens Occupational Health Safety
• Keywords:
  Antioxidation Arsenic-compounds Arsenites Carcinogenesis Carcinogenicity Gene-mutation Mutagenesis
• ISSN:
  0300-8177
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  OSHA Region 3 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  33-45
• Volume:
  255
• Issue:
  1
• NIOSHTIC Number:
  nn:20024211
• Citation:
  Mol Cell Biochem 2004 Jan; 255(1-2):33-45
• Contact Point Address:
  Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, 1095 Willowdale Rd., Morgantown, WV
• Email:
  bhjiang@hsc.wvu.edu
• CAS Registry Number:
  Arsenite (CAS RN 15502-74-6)
• Federal Fiscal Year:
  2004
• Peer Reviewed:
  True
• Source Full Name:
  Molecular and Cellular Biochemistry
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:9bf889defcdaff025ecbae79b97e438f9ef5ec2b571fbb148443dc6b530459d71692b68865111376d7c7e6fb7e2a23d33872996f3ff27ffae2c347e963e81d34
• Download URL:
  https://stacks.cdc.gov/view/cdc/196142/cdc_196142_DS1.pdf
• File Type:
  [PDF - 274.22 KB ]