Administration of isothiocyanate (E-4IB) and cisplatin leads to altered signalling and lysosomal export in human ovarian carcinoma sensitive- and cisplatin-resistant cells

Neoplasma. 2009;56(3):208-14. doi: 10.4149/neo_2009_03_208.

Abstract

The aim of this study was to compare the effect of a new synthetic isothiocyanate derivative, ethyl 4-isothiocyanatobutanoate (E-4IB) and cisplatin (CDDP) in CDDP-sensitive human ovarian carcinoma cell line (A2780) and its resistant subline (A2780/CP). In parental cells, in comparison to untreated cells, sequential administration of both compounds led to higher exosomal dye (LysoTracker Green DND-26) retention and to alterations of mitogen-activated protein kinases (MAPKs), JNK, ERK and p38, or Akt kinase accompanied by changes in several anti- and pro-apoptotic molecules and lysosomal protein LAMP-1, as detected by Western blotting. On the contrary, variant A2780/CP cells were resistant to CDDP- or to combined sensitizer (E-4IB)/inducer (CDDP)-related apoptosis induction and exerted minor changes in the levels of these molecules.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biological Transport / drug effects
  • Cell Line, Tumor
  • Cisplatin / pharmacokinetics
  • Cisplatin / pharmacology*
  • Drug Resistance, Neoplasm
  • Female
  • Humans
  • Isothiocyanates / pharmacology*
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • Lysosomes / metabolism*
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / pathology
  • Signal Transduction / drug effects*

Substances

  • Isothiocyanates
  • isothiocyanic acid
  • JNK Mitogen-Activated Protein Kinases
  • Cisplatin