Antineoplastic cyclic astin analogues kill tumour cells via caspase-mediated induction of apoptosis. (Articolo in rivista)

Type
Label
  • Antineoplastic cyclic astin analogues kill tumour cells via caspase-mediated induction of apoptosis. (Articolo in rivista) (literal)
Anno
  • 2005-01-01T00:00:00+01:00 (literal)
Alternative label
  • Cozzolino, Rosanna; Palladino, Pasquale; Rossi, Filomena; Cali, Gaetano; Benedetti, Ettore; Laccetti, Paolo. (2005)
    Antineoplastic cyclic astin analogues kill tumour cells via caspase-mediated induction of apoptosis.
    in Carcinogenesis (N.Y., Print)
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Cozzolino, Rosanna; Palladino, Pasquale; Rossi, Filomena; Cali, Gaetano; Benedetti, Ettore; Laccetti, Paolo. (literal)
Pagina inizio
  • 733 (literal)
Pagina fine
  • 739 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume
  • 26 (literal)
Rivista
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#descrizioneSinteticaDelProdotto
  • Pubblicazione su rivista scientifica (literal)
Note
  • ISI Web of Science (WOS) (literal)
Titolo
  • Antineoplastic cyclic astin analogues kill tumour cells via caspase-mediated induction of apoptosis. (literal)
Abstract
  • Astins, a family of cyclopentapeptides, isolated from the roots of a medicinal plant Aster tataricus (Compositae), show antitumor activity. Their chem. structures consist of a 16-membered ring system contg. a unique b,g-dichlorinated proline [Pro(Cl2)], other non-coded amino acid residues, and a cis conformation in one of the peptide bonds. The b,g-dichlorinated proline residue is considered to play an important role in their antineoplastic activities in vitro on nasopharynx carcinoma (KB) cells and in vivo on sarcoma 180 ascites and P388 lymphocytic leukemia in mice. The acyclic astins without Pro(Cl2) do not show antitumor activity against S-180 ascites in vivo, suggesting that the cyclic nature of astins plays an important role in their antitumor activities. We synthesized new astin-related cyclopeptides differing from the natural product for the presence of some non-proteinogenic amino acid residues: Aib, Abu, -S(b3)-hPhe and a peptide bond surrogate (-SO2-NH-) and we tested for their antitumor effect. We obsd. cytotoxic effects of the newly synthesized cyclic astins, but not with the acyclic analog astins. We also obsd. that the cyclic astin induced apoptosis in a human papillary thyroid carcinoma cell line (NPA cell line) and that apoptotis was assocd. with activation of caspases. The caspase family inhibitor, Z-Val-Asp-(OMe)-FMK, protected NPA cells from cyclic analog astin-induced apoptosis. To det. which caspase was specifically activated, we assayed caspase activity in astin-treated cells in the presence of specific caspase and 8, 9 or 3 inhibitors, i.e. Z-IETD-FMK, Z-LEHD-FMK Z-DEVD-FMK, which inhibit caspases 8, 9 and 3, resp. The data presented here show selective antineoplastic properties of the newly synthesized cyclic astins, and suggest, for the first time, a mechanism for their antineoplastic action through the activation of apoptotic pathway. (literal)
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