Selected cyclic dipeptides inhibit cancer cell growth and induce apoptosis in HT-29 colon cancer cells

Anticancer Res. 2004 May-Jun;24(3a):1713-9.

Abstract

Background: An increasing number of cyclic dipeptides (CDPs), particularly those containing proline, have been shown to exhibit important biological activity.

Materials and methods: We investigated the potential of seven proline-based CDPs to inhibit cancer cell growth in HT-29, HeLa and MCF-7 cell lines. We also tested whether any of the CDPs were able to induce apoptosis in HT-29 cells.

Results: The SRB assay showed that only cyclo(Phe-Pro) (10 mM) exhibited more than 50% growth inhibition (p<0.01). The MTT assay was used to demonstrate a dose-dependent (0.008-10 mM) growth inhibition by cyclo(Phe-Pro). Hoechst 33342 staining showed that 5 mM cyclo(Phe-Pro) induced chromatin condensation in 18.3+/-2.8% (p<0.01) of HT-29 cells after 72 hours. Furthermore, annexin V binding revealed phosphatidylserine externalisation in cyclo(Phe-Pro)-treated HT-29 cells.

Conclusion: Our findings demonstrate that cyclo(Phe-Pro) inhibits the growth of HT-29, MCF-7 and HeLa cells and induces apoptosis in HT-29 colon cancer cells, suggesting a potential antitumour activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Annexin A5
  • Apoptosis / drug effects*
  • Benzimidazoles
  • Cell Division / drug effects
  • Colonic Neoplasms / drug therapy*
  • Colonic Neoplasms / pathology*
  • Dipeptides / pharmacology*
  • Fluorescein
  • HT29 Cells
  • HeLa Cells
  • Humans
  • Peptides, Cyclic / pharmacology*
  • Proline / analogs & derivatives*
  • Proline / pharmacology
  • Rhodamines
  • Tetrazolium Salts
  • Thiazoles

Substances

  • Annexin A5
  • Benzimidazoles
  • Dipeptides
  • Peptides, Cyclic
  • Rhodamines
  • Tetrazolium Salts
  • Thiazoles
  • lissamine rhodamine B
  • Proline
  • thiazolyl blue
  • bisbenzimide ethoxide trihydrochloride
  • Fluorescein