A novel role for 3, 4-dichloropropionanilide (DCPA) in the inhibition of prostate cancer cell migration, proliferation, and hypoxia-inducible factor 1alpha expression

BMC Cancer. 2006 Aug 2:6:204. doi: 10.1186/1471-2407-6-204.

Abstract

Background: The amide class compound, 3, 4-dichloropropionanilide (DCPA) is known to affect multiple signaling pathways in lymphocyte and macrophage including the inhibition of NF-kappaB ability. However, little is known about the effect of DCPA in cancer cells. Hypoxia-inducible factor 1 (HIF-1) regulates the expression of many genes including vascular endothelial growth factor (VEGF), heme oxygenase 1, inducible nitric oxide synthase, aldolase, enolase, and lactate dehydrogenase A. HIF-1 expression is associated with tumorigenesis and angiogenesis.

Methods: We used Transwell assay to study cell migration, and used immunoblotting to study specific protein expression in the cells.

Results: In this report, we demonstrate that DCPA inhibited the migration and proliferation of DU145 and PC-3 prostate cancer cells induced by serum, insulin, and insulin-like growth factor I (IGF-I). We found that DCPA inhibited HIF-1 expression in a subunit-specific manner in these cancer cell lines induced by serum and growth factors, and decreased HIF-1alpha expression by affecting its protein stability.

Conclusion: DCPA can inhibit prostate cancer cell migration, proliferation, and HIF-1alpha expression, suggesting that DCPA could be potentially used for therapeutic purpose for prostate cancer in the future.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anilides / pharmacology*
  • Cell Movement / drug effects*
  • Cell Proliferation / drug effects*
  • Drug Screening Assays, Antitumor
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / drug effects
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism*
  • Immunoblotting
  • Male
  • Prostatic Neoplasms / drug therapy
  • Prostatic Neoplasms / pathology*
  • Tumor Cells, Cultured

Substances

  • 3,4-dichloropropionanilide
  • Anilides
  • Hypoxia-Inducible Factor 1, alpha Subunit