title: Novel combination of docetaxel and thymoquinone induces synergistic cytotoxicity and apoptosis in DU-145 human prostate cancer cells by modulating PI3K-AKT pathway.
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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Medical Oncology, Izmir Katip Celebi University Ataturk Training and Research Hospital, 35360, Izmir, Turkey, ahmetdirican@yahoo.com.
authors: A
authors: A
authors: Dirican
authors: H
authors: H
authors: Atmaca
authors: E
authors: E
authors: Bozkurt
authors: C
authors: C
authors: Erten
authors: B
authors: B
authors: Karaca
authors: R
authors: R
authors: Uslu
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols; D017209:Apoptosis / Q000187:drug effects*; D016227:Benzoquinones / Q000494:pharmacology*; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects; D000077143:Docetaxel; D004357:Drug Synergism; D006801:Humans; D008297:Male; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D043823:Taxoids / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D016227:Benzoquinones; D043823:Taxoids; D000077143:Docetaxel; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; C003466:thymoquinone