Gene expression analysis of HCT116 colon tumor-derived cells treated with the polyamine analog PG-11047

Natalia A. Ignatenko, Hagit F. Yerushalmi, Ritu Pandey, Karen L. Kachel, David E. Stringer, Laurence J. Marton, Eugene W. Gerner

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Background: The conformationally restricted polyamine analog PG-11047 has significant growth inhibitory activity against prostate and lung cancer cell lines and is currently under evaluation in several clinical trials, both alone and in combination with other drugs, for the treatment of relapsed or refractory cancer. The objective of this study was to identify the molecular signature of genes responsive to PG-11047 treatment and the biochemical effects of this drug in the HCT116 colon cancer cell line. Materials and Methods: Gene expression analysis was performed using Affymetrix GeneChip human genome U133 Plus 2.0 arrays. Changes in protein expression were evaluated using 2D Polyacrylamide gels followed by LCMS/MS. Results: Treatment of cells with PG-11047 at concentrations ranging from 0.1 to 10 μM caused inhibition of cell growth. The activity of PG-11047 was found to correlate with its transcriptional effects on cell cycle control, focal adhesion, adherent and gap junction genes, MAPK-, Wnt- and, TGF-β signaling pathways, transport and DNA/RNA transcription factor genes. PG-11047 caused depletion of poly amine pools. Proteomics analysis showed that PG-11047 restricts the modification of eukaryotic translation initiation factor 5A (eIF5A), resulting in suppression of general protein synthesis in PG-11047-treated cells. Conclusion: These data show that PG-11047 has a broad spectrum of anticancer activity in colon cancer cells.

Original languageEnglish (US)
Pages (from-to)161-176
Number of pages16
JournalCancer Genomics and Proteomics
Volume6
Issue number3
StatePublished - Jan 1 2009

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Keywords

  • Affymetrix gene chip microarray
  • Colon cancer cells
  • PG-11047
  • Polyamine analogs
  • Polyamines

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Ignatenko, N. A., Yerushalmi, H. F., Pandey, R., Kachel, K. L., Stringer, D. E., Marton, L. J., & Gerner, E. W. (2009). Gene expression analysis of HCT116 colon tumor-derived cells treated with the polyamine analog PG-11047. Cancer Genomics and Proteomics, 6(3), 161-176.