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Docetaxel Combined with Thymoquinone Induces Apoptosis in Prostate Cancer Cells via Inhibition of the PI3K/AKT Signaling Pathway

Department of Microbiology, Biochemistry and Immunology, Morehouse School of Medicine, Atlanta, GA 30310, USA
Departments of Pathology and Urology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
Author to whom correspondence should be addressed.
Cancers 2019, 11(9), 1390;
Received: 27 August 2019 / Revised: 9 September 2019 / Accepted: 16 September 2019 / Published: 18 September 2019
(This article belongs to the Special Issue Prostate Cancer: Past, Present, and Future)
Toxicity and the development of resistance by cancer cells are impediments for docetaxel (DTX), a primary drug for treating prostate cancer (PCa). Since the combination of DTX with natural compounds can increase its effectiveness by reducing its toxic concentrations, we evaluated a combination of thymoquinone (TQ) with DTX and determined its cytotoxicity against PCa cells (DU145 and C4-2B). This combination, in a concentration-dependent manner, resulted in synergistic cytotoxicity and apoptosis in comparison to either DTX or TQ alone. In addition, inhibition of cell survival pathways by PI3K/AKT inhibitors conferred sensitivity of DU145 and C4-2B cells to the combination as compared to the individual drugs. Moreover, the combined drugs (DTX+TQ) with inhibitors of PI3K/AKT increased the expression of pro-apoptotic markers (BAX and BID) along with caspase-3, PARP and decreased expression of the anti-apoptotic marker, BCL-XL. These data show that, for PCa cells, the cytotoxic effect of the DTX and TQ combination correlates with a block of the PI3K/AKT signaling pathway. These findings indicate that the combination of DTX and TQ, by blocking of the PI3K/AKT pathway, will improve the survival rate and quality of life of PCa patients. View Full-Text
Keywords: thymoquinone; docetaxel; PI3K/AKT; apoptosis; prostate cancer thymoquinone; docetaxel; PI3K/AKT; apoptosis; prostate cancer
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Singh, S.K.; Apata, T.; Gordetsky, J.B.; Singh, R. Docetaxel Combined with Thymoquinone Induces Apoptosis in Prostate Cancer Cells via Inhibition of the PI3K/AKT Signaling Pathway. Cancers 2019, 11, 1390.

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