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.


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.


CONCLUSIONS
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.
Department of Biochemistry and Microbiology, University of Port Elizabeth, P.O. Box 1600, Port Elizabeth, 6000, South Africa.
Seth Clint
SC
Brauns
Pieter
P
Milne
Ryno
R
Naudé
Maryna
M
Van de Venter
D017304:Annexin A5; D017209:Apoptosis / Q000187:drug effects*; D001562:Benzimidazoles; D002455:Cell Division / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D004151:Dipeptides / Q000494:pharmacology*; D019793:Fluorescein; D019073:HT29 Cells; D006367:HeLa Cells; D006801:Humans; D010456:Peptides, Cyclic / Q000494:pharmacology*; D011392:Proline / Q000031:analogs & derivatives* / Q000494:pharmacology; D012235:Rhodamines; D013778:Tetrazolium Salts; D013844:Thiazoles
D017304:Annexin A5; D001562:Benzimidazoles; D004151:Dipeptides; D010456:Peptides, Cyclic; D012235:Rhodamines; D013778:Tetrazolium Salts; D013844:Thiazoles; C022027:lissamine rhodamine B; D011392:Proline; C022616:thiazolyl blue; C017807:bisbenzimide ethoxide trihydrochloride; D019793:Fluorescein