title: Inhibitory effect of somatostatin Peptide analogues on DNA polymerase activity and human cancer cell proliferation.
abstract: OBJECTIVE
  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.
  
  
  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 α, by these compounds. Compound 2 induced apoptosis of the cells, although compound 3 did not.
  
  
  CONCLUSIONS
  Compounds 2 and 3 had an enhanced anticancer effect based on pol inhibition.
authors.affiliation: Laboratory of Food & Nutritional Sciences, Department of Nutritional Science, Kobe-Gakuin University, Nishi-ku, Kobe, Hyogo 651-2180, Japan.
authors.forename: Isoko
authors.initials: I
authors.lastname: Kuriyama
authors.forename: Anna
authors.initials: A
authors.lastname: Miyazaki
authors.forename: Yuko
authors.initials: Y
authors.lastname: Tsuda
authors.forename: Toshio
authors.initials: T
authors.lastname: Yokoi
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Okada
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Takeuchi
authors.forename: Fumio
authors.initials: F
authors.lastname: Sugawara
authors.forename: Hiromi
authors.initials: H
authors.lastname: Yoshida
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Mizushina
mesh_terms: D000818:Animals; D002417:Cattle; D002453:Cell Cycle / Q000187:drug effects; D048708:Cell Growth Processes / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004273:DNA, Neoplasm / Q000378:metabolism; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism; D045325:HCT116 Cells; D006801:Humans; D008958:Models, Molecular; D019384:Nucleic Acid Synthesis Inhibitors; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D004273:DNA, Neoplasm; D019384:Nucleic Acid Synthesis Inhibitors; D010455:Peptides; D013004:Somatostatin; D004259:DNA-Directed DNA Polymerase