Bromopropane Compounds Increase the Stemness of Colorectal Cancer Cells

Int J Mol Sci. 2017 Sep 1;18(9):1888. doi: 10.3390/ijms18091888.

Abstract

Bromopropane (BP) compounds, including 1-bromopropane, 2-bromopropane, and 1,2-dibromopropane, are used in industry for various purposes, and their deleterious effects on human health are becoming known. In this study, we examined the effects of BP compounds on the stemness of colorectal cancer cells. At low, non-cytotoxic concentrations, BP compounds significantly increased spheroid formation in CSC221, DLD1, Caco2, and HT29 cells. In addition, the levels of cancer stem cell markers, such as aldehyde dehydrogenase-1, cluster of differentiation 133 (CD133), CD44, Lgr5, Musashi-1, Ephrin receptor, and Bmi-1 increased after exposure to BP compounds. BP compounds increased the transcriptional activity of the TOPflash and glioma-associated oncogene homolog zinc finger protein (Gli) promoters in reporter assays and increased the expression of Gli-1, Gli-2, Smoothened (SMO), and β-catenin by RT-PCR. These results demonstrate for the first time that BP compounds have the potential to promote cancer stemness.

Keywords: bromopropane; cancer stem cell; colorectal cancer.

MeSH terms

  • Caco-2 Cells
  • Carcinogens / pharmacology*
  • Carcinogens / toxicity
  • Cell Differentiation / drug effects
  • Cell Differentiation / genetics
  • Colorectal Neoplasms / chemically induced*
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / pathology
  • Gene Expression Regulation, Neoplastic / drug effects
  • HT29 Cells
  • Humans
  • Hydrocarbons, Brominated / pharmacology
  • Hydrocarbons, Brominated / toxicity
  • Neoplasm Proteins / genetics
  • Neoplastic Stem Cells / drug effects*
  • Neoplastic Stem Cells / pathology

Substances

  • Carcinogens
  • Hydrocarbons, Brominated
  • Neoplasm Proteins
  • 1-bromopropane