Salinomycin selectively targets 'CD133+' cell subpopulations and decreases malignant traits in colorectal cancer lines

Ann Surg Oncol. 2011 Jun;18(6):1797-804. doi: 10.1245/s10434-011-1561-2. Epub 2011 Jan 26.

Abstract

Background: Cancer stem-like cells (CSCs) in colorectal cancers (CRC) may account for the failure of treatments because they are resistant to many current anticancer therapies. Salinomycin, a potassium ionophore, was recently identified as a selective inhibitor of breast CSCs.

Methods: The human CRC cell lines HT29 and SW480 were treated with salinomycin and oxaliplatin. Cell viability was determined with cell counting kit 8. Fraction of CD133+ cell subpopulations was assessed by Flow Cytometric analysis. Clonogenecity and migration were determined with soft agar and Boyden chamber assays. Molecular changes were assessed by immunofluorescence staining, RT-PCR, and Western blot analysis.

Results: We report that salinomycin reduces the proportion of CD133+ subpopulations in human CRC HT29 and SW480 cells. Furthermore, salinomycin treatment decreases colony-forming ability and cell motility in HT29 cells. Moreover, salinomycin downregulates the expression of vimentin and induces the E-cadherin expression in HT29 cells.

Conclusions: This study demonstrates the ability of salinomycin to selectively target "CD133+" cell subpopulations and decrease the malignant traits in colorectal cancer lines.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AC133 Antigen
  • Anti-Bacterial Agents / pharmacology*
  • Antigens, CD / genetics
  • Antigens, CD / metabolism*
  • Antineoplastic Agents / pharmacology
  • Blotting, Western
  • Cadherins / genetics
  • Cadherins / metabolism
  • Cell Adhesion / drug effects
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects*
  • Colony-Forming Units Assay
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / metabolism*
  • Drug Therapy, Combination
  • Flow Cytometry
  • Fluorescent Antibody Technique
  • Glycoproteins / genetics
  • Glycoproteins / metabolism*
  • Humans
  • Immunoenzyme Techniques
  • Organoplatinum Compounds / pharmacology
  • Oxaliplatin
  • Peptides / genetics
  • Peptides / metabolism*
  • Pyrans / pharmacology*
  • RNA, Messenger / genetics
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • AC133 Antigen
  • Anti-Bacterial Agents
  • Antigens, CD
  • Antineoplastic Agents
  • Cadherins
  • Glycoproteins
  • Organoplatinum Compounds
  • PROM1 protein, human
  • Peptides
  • Pyrans
  • RNA, Messenger
  • Oxaliplatin
  • salinomycin