Inhibitory effect of somatostatin Peptide analogues on DNA polymerase activity and human cancer cell proliferation.

BACKGROUND AND OBJECTIVES: It was previously reported that ten small peptides derived from TT-232, somatostatin structural analogue (compounds 1-10), synthesised by a solution-phase method, exhibited potent antitumour activity on human epithelial tumour (A431) cells. MATERIALS AND METHODS: The present study investigated the inhibitory activity of these peptide compounds against DNA polymerase (pol) and human cancer cell growth. RESULTS: Among the compounds tested, compounds 1-5, which contain a t-butyloxycarbonyl (Boc) group, inhibited the activity of mammalian pols. Compounds 2 (Boc-Tyr-D-Trp-1-adamantylamide) and 3 (Boc-Tyr-D-Trp-2-adamantylamide) strongly suppressed the growth of a human colon carcinoma (HCT116) cell line and also arrested HCT116 cells in S phase, suggesting that these phenomena observed in cancer cells may be due to the selective inhibition of mammalian pols, especially DNA replicative pol alpha, by these compounds. Compound 2 induced apoptosis of the cells, although compound 3 did not. CONCLUSION: Compounds 2 and 3 had an enhanced anticancer effect based on pol inhibition.