Docetaxel Combined with Thymoquinone Induces Apoptosis in Prostate Cancer Cells via Inhibition of the PI3K/AKT Signaling Pathway
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 th...
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2019-09-01
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doaj-68d8890073f14086bf6b2e1fccda0ae52020-11-25T01:18:49ZengMDPI AGCancers2072-66942019-09-01119139010.3390/cancers11091390cancers11091390Docetaxel Combined with Thymoquinone Induces Apoptosis in Prostate Cancer Cells via Inhibition of the PI3K/AKT Signaling PathwaySantosh Kumar Singh0Tejumola Apata1Jennifer B. Gordetsky2Rajesh Singh3Department of Microbiology, Biochemistry and Immunology, Morehouse School of Medicine, Atlanta, GA 30310, USADepartment of Microbiology, Biochemistry and Immunology, Morehouse School of Medicine, Atlanta, GA 30310, USADepartments of Pathology and Urology, Vanderbilt University Medical Center, Nashville, TN 37232, USADepartment of Microbiology, Biochemistry and Immunology, Morehouse School of Medicine, Atlanta, GA 30310, USAToxicity 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.https://www.mdpi.com/2072-6694/11/9/1390thymoquinonedocetaxelPI3K/AKTapoptosisprostate cancer |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Santosh Kumar Singh Tejumola Apata Jennifer B. Gordetsky Rajesh Singh |
spellingShingle |
Santosh Kumar Singh Tejumola Apata Jennifer B. Gordetsky Rajesh Singh Docetaxel Combined with Thymoquinone Induces Apoptosis in Prostate Cancer Cells via Inhibition of the PI3K/AKT Signaling Pathway Cancers thymoquinone docetaxel PI3K/AKT apoptosis prostate cancer |
author_facet |
Santosh Kumar Singh Tejumola Apata Jennifer B. Gordetsky Rajesh Singh |
author_sort |
Santosh Kumar Singh |
title |
Docetaxel Combined with Thymoquinone Induces Apoptosis in Prostate Cancer Cells via Inhibition of the PI3K/AKT Signaling Pathway |
title_short |
Docetaxel Combined with Thymoquinone Induces Apoptosis in Prostate Cancer Cells via Inhibition of the PI3K/AKT Signaling Pathway |
title_full |
Docetaxel Combined with Thymoquinone Induces Apoptosis in Prostate Cancer Cells via Inhibition of the PI3K/AKT Signaling Pathway |
title_fullStr |
Docetaxel Combined with Thymoquinone Induces Apoptosis in Prostate Cancer Cells via Inhibition of the PI3K/AKT Signaling Pathway |
title_full_unstemmed |
Docetaxel Combined with Thymoquinone Induces Apoptosis in Prostate Cancer Cells via Inhibition of the PI3K/AKT Signaling Pathway |
title_sort |
docetaxel combined with thymoquinone induces apoptosis in prostate cancer cells via inhibition of the pi3k/akt signaling pathway |
publisher |
MDPI AG |
series |
Cancers |
issn |
2072-6694 |
publishDate |
2019-09-01 |
description |
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. |
topic |
thymoquinone docetaxel PI3K/AKT apoptosis prostate cancer |
url |
https://www.mdpi.com/2072-6694/11/9/1390 |
work_keys_str_mv |
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