Induction of apoptosis and stress response in ovarian carcinoma cell lines with ST1926, an atypical retinoid

V. Zuco, C. Zanchi, G. Cassinelli, C. Lanzi, R. Supino, C. Pisano, R. Zanier, V. Giordano, E. Garattini, Franco Zunino

Research output: Contribution to journalArticlepeer-review


To understand the molecular mechanisms mediating apoptosis induction by a novel atypical retinoid, ST1926, the cellular response to drug treatment was investigated in IGROV-1 ovarian carcinoma cells carrying wild-type p53 and a cisplatin-resistant p53 mutant subline (IGROV-1/Pt1). Despite a similar extent of drug-induced DNA strand breaks, the level of apoptosis was substantially higher in p53 wild-type cells. p53 activation and early upregulation of p53-target genes were consistent with p53-dependent apoptosis in IGROV-1 cells. Stress-activated protein kinases were activated in both cell lines in response to ST1926. This event and activation of AP-1 were more pronounced in IGROV-1/Pt1 cells, in which the modulation of DNA repair-associated genes suggests an increased ability to repair DNA damage. Inhibition of JNK or p38 stimulated ST1926-induced apoptosis only in IGROV-1 cells, whereas inhibition of ERKs enhanced apoptosis in both the cell lines. Such a pattern of cellular response and modulation of genes implicated in DNA damage response supports that the genotoxic stress is a critical event mediating drug-induced apoptosis. The results are consistent with apoptosis induction through p53-dependent and - independent pathways, regulated by MAP kinases, which likely play a protective role.

Original languageEnglish
Pages (from-to)280-289
Number of pages10
JournalCell Death and Differentiation
Issue number3
Publication statusPublished - Mar 2004


  • Apoptosis
  • Atypical retinoids
  • DNA damage
  • Stress response

ASJC Scopus subject areas

  • Cell Biology


Dive into the research topics of 'Induction of apoptosis and stress response in ovarian carcinoma cell lines with ST1926, an atypical retinoid'. Together they form a unique fingerprint.

Cite this