Administration of isothiocyanate (E-4IB) and cisplatin leads to altered signalling and lysosomal export in human ovarian carcinoma sensitive- and cisplatin-resistant cells.
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.
Duraj
J
J
Cancer Research Institute, Slovak Academy of Sciences, Slovakia. Jozef.Duraj@savba.sk
Hunakova
L
L
Bodo
J
J
Jakubikova
J
J
Chovancova
J
J
Sedlak
J
J
D001692:Biological Transport / Q000187:drug effects; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000493:pharmacokinetics / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D017879:Isothiocyanates / Q000494:pharmacology*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects*
D017879:Isothiocyanates; C037152:isothiocyanic acid; D048031:JNK Mitogen-Activated Protein Kinases; D002945:Cisplatin