Thymoquinone inhibits IL-7-induced tumor progression and metastatic invasion in prostate cancer cells by attenuating matrix metalloproteinase activity and Akt/NF-κB signaling
Thymoquinone inhibits IL-7-induced tumor progression and metastatic invasion in prostate cancer cells by attenuating matrix metalloproteinase activity and Akt/NF-κB signaling
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DOI：
10.1002/bab.2062
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发表时间：
2020-11-11
影响因子：
2.8
通讯作者：
Rajagopalan, Prasanna
中科院分区：
文献类型：
--
作者：
Alshyarba, Mishari;Otifi, Hassan;Rajagopalan, Prasanna
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Interleukin (IL)-7 acts via the IL-7 receptor in metastatic tumor progression in prostate cancer (PC). The current study aimed to evaluate thymoquinone (Tq), an active constituent from Nigella sativa against IL-7-driven tumor progression and metastatic invasion in PC cells. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to assess the proliferation of PC cells. Enzyme-linked immunosorbent assay was used to detect the expression of IL-7 and matrix metalloproteinases (MMPs). Tumor-cell transendothelial, scratch wound and cell scatter assays were performed to mimic metastasis. Western immunoblotting was used to measure the level of proteins. Tq effectively controlled the proliferation of DU-145, PC-3, and LNCaP cells with GI(50) of 10.18, 12.40, and 16.78 mu M, respectively. IL-7 and IL-7R were natively expressed in all PC types, while maximal expression was detected in DU-145. IL-7 promoted metastatic events, such as transendothelial migration, cell scatter, and cell invasion of DU-145 cells in a dose-dependent manner that was inhibited by Tq. Furthermore, Tq also downregulated p-Akt and NF-kappa B in DU-145 cells induced by IL-7 antibody and reduced the levels of MMP-3 and MMP-7 in these cells in a dose-dependent manner. Collectively, Tq has excellent efficacy in controlling tumor progression, migration, and invasion of DU-145 cells that were driven by the activation of MMPs through IL-7/Akt/NF-kappa B signaling.