Induction of apoptosis and down-regulation of Bcl-XL in cancer cells by a novel small molecule, 2[[3-(2,3-dichlorophenoxy)propyl]amino]ethanol

Cancer Res. 2004 Feb 1;64(3):1110-3. doi: 10.1158/0008-5472.can-03-2790.

Abstract

In a search for new anticancer agents, we identified that 2[[3-(2,3-dichlorophenoxy) propyl]amino]ethanol (2,3-DCPE) induced apoptosis more effectively in various cancer cells than in normal human fibroblasts. We further evaluated the cell-killing effects of this compound in vitro in several human cancer cell lines and normal human fibroblasts. A cell viability assay showed that IC(50)s for human colon cancer cell lines LoVo and DLD-1, for human lung cancer cell lines H1299 and A549, and for normal human fibroblasts were 0.89, 1.95, 2.24, 2.69, and 12.6 micro M, respectively. Subsequent studies revealed that 2,3-DCPE could cause cleavage of caspase-8, caspase-3, caspase-9, and poly(ADP-ribose) polymerase and release of cytochrome c in cancer cells but not in normal human fibroblasts. Our data also showed that 2,3-DCPE attenuated the protein level of Bcl-XL and that apoptosis induction by 2,3-DCPE could be blocked by enforced overexpression of Bcl-XL. Our results suggest that 2,3-DCPE might be a potential new anticancer agent.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Cell Division / drug effects
  • Cell Line, Tumor
  • Chlorobenzenes / pharmacology*
  • Down-Regulation / drug effects
  • Drug Screening Assays, Antitumor
  • Ethanolamines / pharmacology*
  • Fibroblasts / drug effects
  • Humans
  • Proto-Oncogene Proteins c-bcl-2 / biosynthesis*
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Transfection
  • bcl-X Protein

Substances

  • 2-((3-(2,3-dichlorophenoxy)propyl)amino)ethanol
  • Antineoplastic Agents
  • BCL2L1 protein, human
  • Chlorobenzenes
  • Ethanolamines
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-X Protein