Document Detail

Human larynx carcinoma cells resistant to cis-diamminedichloroplatinum(II): mechanisms involved in the resistance.
MedLine Citation:
PMID:  7935985     Owner:  NLM     Status:  MEDLINE    
The aim of this study was to characterize two cis-diamminedichloroplatinum(II) (CDDP) resistant cell lines established from human larynx carcinoma HEp2 cells through repeated treatments with increased CDDP concentrations. CK2 cells obtained by continuous treatments were more resistant to CDDP than CA3 cells obtained by acute treatments. The examination of growth characteristics showed that both CDDP resistant cells had doubling times identical to that of the parental cells, but had lower plating efficiency. The possible involvement of glutathione (GSH), glutathione transferases (GST), metallothioneins, P-glycoprotein and drug accumulation in CDDP resistance was examined. Glutathione contents were elevated in both CDDP resistant lines. However, neither GSH nor GST were involved in CDDP resistance. This was demonstrated by simultaneous incubation of parental and CDDP resistant cells with CDDP and specific inhibitors of GSH and GST alpha and pi (buthionine sulfoximine and ethacrinic acid). Similarly, verapamil, an inhibitor of P-glycoprotein, did not influence the sensitivity of parental and resistant cells to CDDP. As compared to the parental cells, CK2 cells became resistant and CA3 cells became sensitive to cadmium, indicating increased level of metallothioneins in CK2 cells, and reduced level in CA3 cells. Measurements of platinum contents in parental and CDDP resistant cells after 1, 3 and 6 hours exposure to 70 mumol CDDP showed reduction in platinum accumulation after each exposure time in CK2 cells, and after 6 hours exposure in CA3 cells. This study identified decreased platinum accumulation as an important mechanism of CDDP resistance in human larynx carcinoma cells.
L Beketić-Oresković; M Osmak; M Jaksić
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Neoplasma     Volume:  41     ISSN:  0028-2685     ISO Abbreviation:  Neoplasma     Publication Date:  1994  
Date Detail:
Created Date:  1994-11-17     Completed Date:  1994-11-17     Revised Date:  2004-11-17    
Medline Journal Info:
Nlm Unique ID:  0377266     Medline TA:  Neoplasma     Country:  CZECH REPUBLIC    
Other Details:
Languages:  eng     Pagination:  163-9     Citation Subset:  IM    
Ruder Bosković Institute, Zagreb, Croatia.
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MeSH Terms
Buthionine Sulfoximine
Cadmium / pharmacology
Cadmium Chloride
Cell Cycle / physiology
Chlorides / pharmacology
Cisplatin / pharmacokinetics,  pharmacology*
Clone Cells
Drug Resistance / physiology
Ethacrynic Acid / pharmacology
Glutathione / metabolism
Laryngeal Neoplasms / drug therapy*,  metabolism,  pathology*
Methionine Sulfoximine / analogs & derivatives,  pharmacology
Tumor Cells, Cultured / drug effects
Reg. No./Substance:
0/Chlorides; 10108-64-2/Cadmium Chloride; 15663-27-1/Cisplatin; 1982-67-8/Methionine Sulfoximine; 5072-26-4/Buthionine Sulfoximine; 58-54-8/Ethacrynic Acid; 70-18-8/Glutathione; 7440-43-9/Cadmium

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