The anticancer effects of sodium selenite and selenomethionine on human colorectal carcinoma cell lines in nude mice

Oncol Res. 2009;18(1):1-8. doi: 10.3727/096504009789745647.

Abstract

The studies were carried out on nude mice bearing human colorectal carcinoma SW480 cell line xenografts to evaluate the chemotherapeutic potential of selenium containing compounds such as sodium selenite (SSe) and selenomethionine (SeMet). Three doses of anticancer drugs were used, including 0.1 mg/kg/day SSe (LSSe), 2 mg/kg/day SSe (HSSe), and 2 mg/kg/day SeMet. We explored the anticancer effect of SSe and SeMet administered by IP injection for 21 days. We observed the pathologic changes and the cell apoptosis in tumor tissue by HE staining and TUNNEL assay after HSSe and SeMet treatment. GSH level and antioxidant enzyme GPX activity in tumor tissues were assessed. In addition, Western blotting was used to detect the expression of apoptosis-related proteins. The results suggested that HSSe and SeMet had significantly inhibited tumor growth in vivo. We also observed the pathologic changes and cell apoptosis in tumor tissues after HSSe and SeMet treatment. GSH level was a bit increased but the GPX activity was reduced. Moreover, SSe and SeMet treatment downregulated the expression of the protein Bcl-xL, increased the expression of Bax, Bad, and Bim, and activated caspase-9. SSe and SeMet may be the selective, low-toxic anticancer agents to treat human colorectal carcinoma cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Apoptosis Regulatory Proteins / metabolism
  • Bcl-2-Like Protein 11
  • Body Weight / drug effects
  • Caspase 9 / metabolism
  • Cell Line, Tumor
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / pathology*
  • Female
  • Gene Expression / drug effects
  • Glutathione / metabolism
  • Glutathione Peroxidase / metabolism
  • Humans
  • Membrane Proteins / metabolism
  • Mice
  • Mice, Nude
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Selenomethionine / administration & dosage
  • Selenomethionine / pharmacology
  • Selenomethionine / therapeutic use*
  • Sodium Selenite / administration & dosage
  • Sodium Selenite / pharmacology
  • Sodium Selenite / therapeutic use*
  • Xenograft Model Antitumor Assays*
  • bcl-2-Associated X Protein / metabolism
  • bcl-Associated Death Protein / metabolism
  • bcl-X Protein / metabolism

Substances

  • Apoptosis Regulatory Proteins
  • BAD protein, human
  • BCL2L1 protein, human
  • BCL2L11 protein, human
  • Bcl-2-Like Protein 11
  • Bcl2l11 protein, mouse
  • Membrane Proteins
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-2-Associated X Protein
  • bcl-Associated Death Protein
  • bcl-X Protein
  • Selenomethionine
  • Glutathione Peroxidase
  • Caspase 9
  • Glutathione
  • Sodium Selenite