title: A new tellurium-containing amphiphilic molecule induces apoptosis in HCT116 colon cancer cells.
abstract: BACKGROUND
  Chalcogen-based redox modulators over the years have attracted considerable attention as anti-cancer agents. New selenium- and tellurium-containing compounds with a polar head group and aryl-groups of various lengths have recently been reported as biologically active in several organisms. In the present study, we used the most active of the tellurium compound DP41, and its selenium counterpart DP31 to investigate their effects on the human cancer cell line HCT116.
  
  
  METHODS
  Cells were treated with DP41 or DP31 and the formation of superoxide radicals was determined using dihydroethidium. Cell cycle analysis and apoptosis was determined by cytofluorimetry. Proteins involved in ER signaling and apoptosis were determined by Western blot analysis and fluorescence microscopy.
  
  
  RESULTS
  With 50μM of DP41, we observed an increase in O2(-) formation. There was, however, no such increase in O2(-) after treatment with the corresponding selenium compound under the same conditions. In the case of DP41, the production of O2(-) radicals was followed by an up-regulation of Nrf2, HO-1, phospho-eIF2α and ATF4. CHOP was also induced and cells entered apoptosis. Unlike the cancer cells, normal retinal epithelial ARPE-19 cells did not produce elevated levels of O2(-) radicals nor did they induce the ER signaling pathway or apoptosis.
  
  
  CONCLUSIONS
  The tellurium-containing compound DP41, in contrast to the corresponding selenium compound, induces O2(-) radical formation and oxidative and ER stress responses, including CHOP activation and finally apoptosis.
  
  
  CONCLUSIONS
  These results indicate that DP41 is a redox modulating agent with promising anti-cancer potentials.
authors: Medical Biochemistry and Molecular Biology, University of the Saarland, Building 44, D-66424 Homburg, Germany; Bioorganic Chemistry, University of the Saarland, P.O. Box 151150, D-66123 Saarbrücken, Germany.
authors: Peng
authors: P
authors: Du
authors: Medical Biochemistry and Molecular Biology, University of the Saarland, Building 44, D-66424 Homburg, Germany.
authors: Nathaniel Edward Bennett
authors: NE
authors: Saidu
authors: Medical Biochemistry and Molecular Biology, University of the Saarland, Building 44, D-66424 Homburg, Germany.
authors: Johanna
authors: J
authors: Intemann
authors: Bioorganic Chemistry, University of the Saarland, P.O. Box 151150, D-66123 Saarbrücken, Germany.
authors: Claus
authors: C
authors: Jacob
authors: Medical Biochemistry and Molecular Biology, University of the Saarland, Building 44, D-66424 Homburg, Germany. Electronic address: M.Montenarh@mx.uni-saarland.de.
authors: Mathias
authors: M
authors: Montenarh
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D059865:Endoplasmic Reticulum Stress; D045325:HCT116 Cells; D051547:Heme Oxygenase-1 / Q000378:metabolism; D006801:Humans; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D013691:Tellurium / Q000494:pharmacology*; D051742:Transcription Factor CHOP / Q000032:analysis / Q000502:physiology
chemical_list: D000970:Antineoplastic Agents; C497249:DDIT3 protein, human; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D013481:Superoxides; D051742:Transcription Factor CHOP; D051547:Heme Oxygenase-1; D013691:Tellurium
keywords: Apoptosis; Cancer cell; Endoplasmic reticulum stress pathway; Non-cancer cell; Reactive oxygen species