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In vitro cytotoxicity of novel platinum-based drugs and dichloroacetate against lung carcinoid cell lines.
MedLine Citation:
PMID:  21239354     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
Introduction Chemotherapy for advanced well-differentiated carcinoids is characterised by low response rates and short duration of responses. The present study aimed to assess the in vitro activity of novel platinum-based chemotherapeutic drugs in combination with dichloroacetate (DCA), a sensitiser to apoptosis, against lung carcinoid cell lines. Methods Three permanent cell lines (UMC-11, H727 and H835) were exposed to 14 different established cytotoxic drugs and the novel platinum-based compounds as satraplatin, JM118 and picoplatin in combination with DCA, and viability of the cells was measured using a tetrazoliumbased dye assay. Results With exception of the highly chemoresistant UMC- 11 line, the carcinoid cell lines (H727, H835) were sensitive to the majority of chemotherapeutics in vitro. Among the platinum-based drugs, carboplatin and oxaliplatin showed highest efficacy. H835 cells growing as multicellular spheroids were 2.7-8.7-fold more resistant to picoplatin, satraplatin and its metabolite compared to single cell suspensions. DCA (10 mM) inhibited the growth of UMC- 11 cells by 22% and sensitised these highly resistant cells to carboplatin, satraplatin and JM118 1.4-2.4-fold. Conclusion The highly resistant UMC-11 lung carcinoid cells are sensitive to carboplatin, oxaliplatin and the satraplatin metabolite JM118, but multicellular spheroidal growth, as observed in the H835 cell line and pulmonary tumourlets, seems to increase chemoresistance markedly. The activity of carboplatin and JM118 is significantly and specifically increased in combination with the apoptosis sensitiser DCA that promotes mitochondrial respiration over aerobic glycolysis. In summary, among the novel platinum drugs satraplatin has the potential for treatment of lung carcinoids and DCA potentiates the cytotoxicity of selected platinum drugs.
Authors:
W Fiebiger; U Olszewski; E Ulsperger; K Geissler; G Hamilton
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico     Volume:  13     ISSN:  1699-3055     ISO Abbreviation:  Clin Transl Oncol     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2011-01-17     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101247119     Medline TA:  Clin Transl Oncol     Country:  Spain    
Other Details:
Languages:  eng     Pagination:  43-9     Citation Subset:  IM    
Affiliation:
Department of Internal Medicine I, Division of Oncology, St. Poelten Hospital, St. Poelten, Austria.
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