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Molecular and Cellular Biochemistry

, Volume 394, Issue 1–2, pp 209–215 | Cite as

Berberine diminishes side population and down-regulates stem cell-associated genes in the pancreatic cancer cell lines PANC-1 and MIA PaCa-2

  • S. H. Park
  • J. H. Sung
  • N. ChungEmail author
Article

Abstract

Cancer stem cells play an important role in metastasis and the relapse of drug resistant cancers. Side-population (SP) cells are capable of effluxing Hoechst 33342 dye and are referred to as cancer stem cells. We investigated the effect of berberine on pancreatic cancer stem cells of PANC-1 and MIA PaCa-2. For both cell lines, the proportions of SP cells in the presence of berberine were investigated and compared to the proportions in the presence of gemcitabine, a standard pancreatic anti-cancer drug. The proportions of SP cells in the PANC-1 and MIA PaCa-2 cell lines were about 9 and <0.1 %, respectively. After berberine and gemcitabine treatments, the SP cell proportion of PANC-1 decreased to 5.7 ± 2.0 and 6.8 ± 0.8 %, respectively, which compares to the control proportion of (9.7 ± 1.7). After berberine and gemcitabine treatment of PANC-1, of the four stem cell-associated genes (SOX2, POU5F1, NANOG, and NOTCH1), all but NOTCH1 were down-regulated. Unfortunately, the effect of berberine and gemcitabine treatments on MIA PaCa-2 SP cells could not be clearly observed because SP cells represented only a very small proportion of MIA PaCa-2 cells. However, SOX2, POU5F1, and NANOG genes were shown to be effectively down-regulated in the MIA PaCa-2 cell line as a whole. Taken together, these results indicate that berberine is as effective at targeting pancreatic cancer cell lines as gemcitabine. Therefore, we believe that POU5F1, SOX2, and NANOG can serve as potential markers, and berberine may be an effective anti-cancer agent when targeting human pancreatic cancer cells and/or their cancer stem cells.

Keywords

Pancreatic cancer Cancer stem cells Side population Berberine POU5F1 NANOG 

Notes

Acknowledgments

This study was supported by a Grant (B110053) from the Korea Health Technology R&D Project, Ministry of Health and Welfare, and a grant from Korea University.

Conflict of interest

The authors declare that no conflicts of interest exist.

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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.Department of Biosystems and Biotechnology, College of Life Sciences and BiotechnologyKorea UniversitySeoulKorea
  2. 2.Biomedical Research InstituteSeoul National University HospitalSeoulKorea

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