Clinical and Translational Oncology

, Volume 17, Issue 2, pp 145–151

Novel combination of docetaxel and thymoquinone induces synergistic cytotoxicity and apoptosis in DU-145 human prostate cancer cells by modulating PI3K–AKT pathway

  • A. Dirican
  • H. Atmaca
  • E. Bozkurt
  • C. Erten
  • B. Karaca
  • R. Uslu
Research Article

Abstract

Background

The treatment of castrate-resistant prostate cancer (CRPC) still remains as an important challenge of daily oncology practice. Docetaxel significantly prolongs overall survival in men with CRPC. Thymoquinone (TQ), one of the flavonoid compounds isolated from Nigealla sativa, has been shown to possess cytotoxic activity against a variety of cancer cell lines.

Materials and Methods

The aim of the study was to investigate the possible synergistic cytotoxic/apoptotic effects of a novel combination, docetaxel and TQ in DU-145 hormone- and drug-refractory prostate cancer cells and their effects on PI3K and ERK signaling pathways.

Results

We observed that the combination of docetaxel and TQ resulted in a significant synergistic cytotoxicy and apoptosis as compared to any single agent alone, in a dose-dependent manner. It was found that viability of the combination treated cells was not significantly changed in the presence of LY294002 as compared to inhibitor treated cells. However, in the presence of FR180204, viability of combination treated cells was significantly decreased as compared to inhibitor treated cells. In conclusion, cytotoxic effect of the docetaxel and TQ combination is correlated with the block of the PI3K/Akt signaling pathway in DU-145 cells.

Conclusion

Therefore, this combination strategy may be an alternative approach for the challenging era of daily oncologic practice. Also, the combination of docetaxel and TQ might allow a reduction in docetaxel doses and diminish adverse effects of docetaxel while maintaining the therapeutic effect in patients with CRPC.

Keywords

Thymoquinone Docetaxel Prostate cancer Combination treatment PI3K/Akt signaling pathways 

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Copyright information

© Federación de Sociedades Españolas de Oncología (FESEO) 2014

Authors and Affiliations

  • A. Dirican
    • 1
  • H. Atmaca
    • 2
  • E. Bozkurt
    • 2
  • C. Erten
    • 1
  • B. Karaca
    • 3
  • R. Uslu
    • 3
  1. 1.Department of Medical OncologyIzmir Katip Celebi University Ataturk Training and Research HospitalIzmirTurkey
  2. 2.Section of Molecular Biology, Department of Biology, Faculty of Science and ArtsCelal Bayar UniversityManisaTurkey
  3. 3.Division of Medical Oncology, Tulay Aktas Oncology Hospital, School of MedicineEge UniversityIzmirTurkey

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