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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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| Published in: | British journal of cancer 2006-11, Vol.95 (10), p.1348-1353 |
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| Main Authors: | , , , , , , |
| Format: | Article |
| Language: | English |
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| cited_by | cdi_FETCH-LOGICAL-c485t-18fc1eb0542af356bf3eda338677fb9ddff6803141ffc4f862675088061cecd23 |
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| cites | cdi_FETCH-LOGICAL-c485t-18fc1eb0542af356bf3eda338677fb9ddff6803141ffc4f862675088061cecd23 |
| container_end_page | 1353 |
| container_issue | 10 |
| container_start_page | 1348 |
| container_title | British journal of cancer |
| container_volume | 95 |
| creator | Bodo, J Hunakova, L Kvasnicka, P Jakubikova, J Duraj, J Kasparkova, J Sedlak, J |
| description | 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. |
| doi_str_mv | 10.1038/sj.bjc.6603434 |
| format | article |
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α
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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.</description><subject>Antineoplastic Agents - pharmacology</subject><subject>Apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>Biological and medical sciences</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Biophysics</subject><subject>Blotting, Western</subject><subject>Butyrates - pharmacology</subject><subject>Cancer Research</subject><subject>Cancer therapies</subject><subject>Caspase 3 - metabolism</subject><subject>Cell cycle</subject><subject>Cell Cycle Proteins - metabolism</subject><subject>Cell Proliferation - drug effects</subject><subject>Cisplatin - pharmacology</subject><subject>Cooperation</subject><subject>Drug Resistance</subject><subject>Drug Synergism</subject><subject>Drug Therapy, Combination</subject><subject>Epidemiology</subject><subject>Female</subject><subject>Glutathione</subject><subject>Humans</subject><subject>Isothiocyanates - 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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.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>17060935</pmid><doi>10.1038/sj.bjc.6603434</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| 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 |
| title | Sensitisation for cisplatin-induced apoptosis by isothiocyanate E-4IB leads to signalling pathways alterations |
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