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

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.

• Authors: J Duraj, L Hunakova, J Bodo, J Jakubikova, J Chovancova, J Sedlak
• Journal: Neoplasma (Neoplasma) Vol. 56 Issue 3 Pg. 208-14 ( 2009) ISSN: 0028-2685 [Print] Slovakia
• PMID: 19309223 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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