Clinical and Translational Oncology

, Volume 13, Issue 1, pp 43–49 | Cite as

In vitro cytotoxicity of novel platinum-based drugs and dichloroacetate against lung carcinoid cell lines

  • Wolfgang Fiebiger
  • Ulrike Olszewski
  • Ernst Ulsperger
  • Klaus Geissler
  • Gerhard Hamilton
Research Articles

Abstract

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.

Keywords

Carcinoid Chemosensitivity Drug resistance Platinum complex Picoplatin Satraplatin Dichloroacetate 

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Copyright information

© Feseo 2011

Authors and Affiliations

  • Wolfgang Fiebiger
    • 1
  • Ulrike Olszewski
    • 2
  • Ernst Ulsperger
    • 2
  • Klaus Geissler
    • 2
  • Gerhard Hamilton
    • 2
    • 3
  1. 1.Department of Internal Medicine I Division of OncologySt. Poelten HospitalSt. PoeltenAustria
  2. 2.Ludwig Boltzmann Cluster of Translational OncologyViennaAustria
  3. 3.Department of SurgeryMedical University ViennaViennaAustria

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