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

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.