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    Induction of Autophagic Cell Death by Thymoquinone in Docetaxel Resistant Prostate Cancer Cells
    (2021) Oguz, Ferdi; İlhan, Suleyman
    Aim: Acquired docetaxel (DOC) resistance of prostate cancer (PCa) is still a clinical problem. In addition to failure in chemotherapy treatment, it causes tumor recurrence. Therefore, novel and more effective compounds are needed in DOC-resistant PCa treatment. This study aimed to investigate the possible cytotoxic and cell death-inducing activities of thymoquinone (TQ), one of the main active components of Nigella sativa L., on DOC-resistant prostate cancer cells. Material and Methods: DOC-resistant PC3 cells (DOC-R/PC3) were developed by the continuous culture with increment concentrations of DOC (1-10 nM) until they improved their growth and division abilities. The cell viability was determined by MTT assay. The MuseTM Annexin V & Dead Cell kit was performed to detect apoptotic cell death. Autophagic vacuoles were observed by staining autophagic vacuoles. The levels of LC3I, LC3II and Beclin-1 proteins were investigated via western blot analysis. Results: TQ inhibited the viability of DOC-R/PC3 cells in a dose- and time-dependent manner (p=0.014). The IC50 value of TQ for DOC-R/PC3 cells was calculated as 60 µM at 72 h. Treatment of TQ did not induce apoptotic cell death in DOC-resistant prostate cancer cells but induced the formation of autophagic vacuoles. Moreover, Beclin-1 and LC3-II protein levels were increased in TQ-treated DOC-R/PC3 cells, however, LC3-I levels were decreased in DOC-R/PC3 cells. Conclusion: All these results show that TQ may become a new therapeutic target for DOC-resistant prostate cancer in the future.