Sensitisation for cisplatin-induced apoptosis by isothiocyanate E-4IB leads to signalling pathways alterations

A new synthetic isothiocyanate (ITC) derivative, ethyl 4-isothiocyanatobutanoate (E-4IB), appeared to be an effective modulator of cellular proliferation and potent inducer of apoptosis. In cooperation with cisplatin, this compound exerted synergistic effects in human ovarian carcinoma A2780 cells....

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Bibliographic Details
Published in:British journal of cancer 2006-11, Vol.95 (10), p.1348-1353
Main Authors: Bodo, J, Hunakova, L, Kvasnicka, P, Jakubikova, J, Duraj, J, Kasparkova, J, Sedlak, J
Format: Article
Language:English
Subjects:
Antineoplastic Agents - pharmacology
Apoptosis
Apoptosis - drug effects
Biological and medical sciences
Biomedical and Life Sciences
Biomedicine
Biophysics
Blotting, Western
Butyrates - pharmacology
Cancer Research
Cancer therapies
Caspase 3 - metabolism
Cell cycle
Cell Cycle Proteins - metabolism
Cell Proliferation - drug effects
Cisplatin - pharmacology
Cooperation
Drug Resistance
Drug Synergism
Drug Therapy, Combination
Epidemiology
Female
Glutathione
Humans
Isothiocyanates - pharmacology
Kinases
Medical research
Medical sciences
Membrane Potentials - drug effects
Mitochondria - drug effects
Molecular Medicine
Oncology
Ovarian cancer
Ovarian Neoplasms - drug therapy
Ovarian Neoplasms - pathology
Protein Kinases - metabolism
Proteins
Signal transduction
Signal Transduction - drug effects
Translational Therapeutics
Tumor Cells, Cultured
Tumors
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Summary:A new synthetic isothiocyanate (ITC) derivative, ethyl 4-isothiocyanatobutanoate (E-4IB), appeared to be an effective modulator of cellular proliferation and potent inducer of apoptosis. In cooperation with cisplatin, this compound exerted synergistic effects in human ovarian carcinoma A2780 cells. In the present study we investigated in more detail E4IB-sensitisation for cisplatin-induced apoptosis. Sequential administration of both cytostatic agents led to increased intracellular platinum accumulation, glutathione level depletion and mitochondrial membrane potential dissipation. These events were accompanied with poly (ADP-ribosyl) polymerase cleavage, stimulation of caspase-3 activity, upregulation of p53, FasL and Gadd45 α , cyclin B1 downregulation and an increase in mitogen-activated protein kinases JNK, ERK and p38 phosphorylation as well as PI3K level alterations. The presented results might have implications for developing new strategies aimed at therapeutic benefit of natural or synthetic ITCs in cooperation with various anticancer drugs.
ISSN:0007-0920
1532-1827
DOI:10.1038/sj.bjc.6603434