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

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

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
Volume13
Issue number10
DOIs
Publication statusPublished - Sep 11 2001

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Keywords

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

ASJC Scopus subject areas

  • Cell Biology

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