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.