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Investigational New Drugs

, Volume 27, Issue 2, pp 99–110 | Cite as

Sulfinosine enhances doxorubicin efficacy through synergism and by reversing multidrug resistance in the human non-small cell lung carcinoma cell line (NCI-H460/R)

  • Milica Pešić
  • Tijana Andjelković
  • Jasna Banković
  • Ivanka D. Marković
  • Ljubiša Rakić
  • Sabera RuždijićEmail author
PRECLINICAL STUDIES

Summary

A resistant non-small cell lung carcinoma cell line—NSCLC (NCI-H460/R) was established in order to investigate the potential of sulfinosine (SF) to overcome multidrug resistance (MDR). The cytotoxicity of doxorubicin (DOX) in NCI-H460/R cells was enhanced by interaction with SF. SF improved the sensitivity of resistant cells to DOX when NCI-H460/R cells were pretreated with SF. Synergism was accompanied by the accumulation of cells in S and G2/M phases. Pretreatment with SF was more potent in improving the sensitivity to DOX than verapamil (VER). The decrease of mdr1 and topo II α expression (assessed by RT-PCR), was consistent with the DOX accumulation assay and cell cycle analysis. Also, SF significantly decreased intracellular glutathione (GSH) concentration. These results point to SF as a potential agent of MDR reversal and a valuable drug for improving chemotherapy of NSCLC.

Keywords

NSCLC Multidrug Resistance, Sulfinosine Doxorubicin Drug Combination, Glutathione 

Notes

Acknowledgement

This study was supported by grant #143009B from the Ministry of Science, Republic of Serbia.

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Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Milica Pešić
    • 1
  • Tijana Andjelković
    • 1
  • Jasna Banković
    • 1
  • Ivanka D. Marković
    • 2
  • Ljubiša Rakić
    • 3
  • Sabera Ruždijić
    • 1
    • 4
    Email author
  1. 1.Institute for Biological Research, Department of NeurobiologyUniversity of BelgradeBelgradeRepublic of Serbia
  2. 2.Faculty of MedicineUniversity of BelgradeBelgradeRepublic of Serbia
  3. 3.Serbian Academy of Sciences and ArtsBelgradeRepublic of Serbia
  4. 4.Institute for Biological Research, Department of Neurobiology, Laboratory of Molecular NeurobiologyUniversity of BelgradeBelgradeRepublic of Serbia

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