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

Cell Death Differ. 2004 Mar;11(3):280-9. doi: 10.1038/sj.cdd.4401304.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adamantane / analogs & derivatives
  • Adamantane / pharmacology*
  • Adamantane / toxicity
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / toxicity
  • Apoptosis / drug effects*
  • Blotting, Western
  • Carcinoma / drug therapy*
  • Carcinoma / genetics
  • Carcinoma / metabolism
  • Carcinoma / pathology
  • Caspases / drug effects
  • Caspases / metabolism
  • Cell Division / drug effects
  • Cell Line, Tumor
  • Cinnamates / pharmacology*
  • Cinnamates / toxicity
  • DNA Damage / drug effects
  • DNA Repair
  • DNA, Neoplasm / analysis
  • DNA, Neoplasm / drug effects
  • Enzyme Activation / drug effects
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • Mitogen-Activated Protein Kinases / drug effects
  • Mitogen-Activated Protein Kinases / metabolism
  • Molecular Structure
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / pathology
  • Proliferating Cell Nuclear Antigen / metabolism
  • Stress, Physiological*
  • Transcription Factor AP-1 / metabolism
  • Tumor Suppressor Protein p53 / metabolism


  • 3-(4'-hydroxy-3'-adamantylbiphenyl-4-yl)acrylic acid
  • Antineoplastic Agents
  • Cinnamates
  • DNA, Neoplasm
  • Proliferating Cell Nuclear Antigen
  • Transcription Factor AP-1
  • Tumor Suppressor Protein p53
  • Mitogen-Activated Protein Kinases
  • Caspases
  • Adamantane