The somatostatin analogue TT-232 induces apoptosis in A431 cells - Sustained activation of stress-activated kinases and inhibition of signalling to extracellular signal-regulated kinases

Tibor Vántus, György Kéri, Zita Krivickiene, Mindaugas Valius, Attila Steták, Stefaan Keppens, Péter Csermely, Pál I. Bauer, Gyöngyi Bökönyi, Wim Declercq, Peter Vandenabeele, Wilfried Merlevede, Jackie R. Vandenheede

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TT-232 is a somatostatin analogue containing a five-residue ring structure. The present report describes TT-232-induced signalling events in A431 cells, where a 4-h preincubation with the peptide irreversibly induced a cell death program, which involves DNA-laddering and the appearance of shrunken nuclei, but is unrelated to somatostatin signalling. Early intracellular signals of TT-232 include a transient two-fold activation of the extracellular signal-regulated kinase (ERK2) and a strong and sustained activation of the stress-activated protein kinases c-Jun NH2-terminal kinase (JNK)/SAPK and p38MAPK. Blocking the signalling to ERK or p38MAPK activation had no effect on the TT-232-induced cell killing. At the commitment time for inducing cell death, TT-232 decreased EGFR-tyrosine phosphorylation and prevented epidermial growth factor (EGF)-induced events like cRaf-1 and ERK2 activation. Signalling to ERK activation by FCS, phorbol 12-myristate 13-acetate (PMA) and platelet-derived growth factor (PDGF) was similarly blocked. Our data suggest that TT-232 triggers an apoptotic type of cell death, concomitant with a strong activation of JNK and a blockade of cellular ERK2 activation pathways.

Original languageEnglish
Pages (from-to)717-725
Number of pages9
JournalCellular Signalling
Issue number10
Publication statusPublished - Sep 11 2001



  • A431 cells
  • Antitumour effect
  • Apoptosis
  • MAPKinases
  • Somatostatin-analog

ASJC Scopus subject areas

  • Cell Biology

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