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

dc.contributor.authorDirican A.
dc.contributor.authorAtmaca H.
dc.contributor.authorBozkurt E.
dc.contributor.authorErten C.
dc.contributor.authorKaraca B.
dc.contributor.authorUslu R.
dc.date.accessioned2024-07-22T08:13:52Z
dc.date.available2024-07-22T08:13:52Z
dc.date.issued2015
dc.description.abstractBackground: 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. © 2014, Federación de Sociedades Españolas de Oncología (FESEO).
dc.identifier.DOI-ID10.1007/s12094-014-1206-6
dc.identifier.issn1699048X
dc.identifier.urihttp://akademikarsiv.cbu.edu.tr:4000/handle/123456789/16431
dc.language.isoEnglish
dc.publisherSpringer-Verlag Italia s.r.l.
dc.subjectAntineoplastic Agents
dc.subjectAntineoplastic Combined Chemotherapy Protocols
dc.subjectApoptosis
dc.subjectBenzoquinones
dc.subjectBlotting, Western
dc.subjectCell Proliferation
dc.subjectDrug Synergism
dc.subjectHumans
dc.subjectMale
dc.subjectPhosphatidylinositol 3-Kinases
dc.subjectProstatic Neoplasms
dc.subjectProto-Oncogene Proteins c-akt
dc.subjectSignal Transduction
dc.subjectTaxoids
dc.subjectTumor Cells, Cultured
dc.subjectantineoplastic agent
dc.subjectbenzoquinone derivative
dc.subjectdocetaxel
dc.subjectphosphatidylinositol 3 kinase
dc.subjectprotein kinase B
dc.subjecttaxoid
dc.subjectthymoquinone
dc.subjectapoptosis
dc.subjectcell proliferation
dc.subjectdrug effects
dc.subjectdrug potentiation
dc.subjecthuman
dc.subjectmale
dc.subjectmetabolism
dc.subjectpathology
dc.subjectProstatic Neoplasms
dc.subjectsignal transduction
dc.subjecttumor cell culture
dc.subjectWestern blotting
dc.titleNovel combination of docetaxel and thymoquinone induces synergistic cytotoxicity and apoptosis in DU-145 human prostate cancer cells by modulating PI3K–AKT pathway
dc.typeArticle

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