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Resveratrol induces depletion of TRAF6 and suppresses prostate cancer cell proliferation and migration.
The International Journal of Biochemistry & Cell Biology ( IF 4 ) Pub Date : 2019-11-09 , DOI: 10.1016/j.biocel.2019.105644
Farjana Yeasmin Khusbu 1 , Xi Zhou 1 , Mridul Roy 2 , Fang-Zhi Chen 3 , Qian Cao 1 , Han-Chun Chen 1
Affiliation  

Although the early diagnosis of prostate cancer (PCa) enhances life expectancy with a 5-year survival rate of 100 %, metastasized-PCa is the fundamental reason for death by PCa, hence requires an advanced and target-directed treatment strategy. Metastasis is considered to be initiated with the epithelial-mesenchymal transition (EMT) event in which tumor cells change their epithelial characteristics into mesenchymal form and exacerbates the cancer progression. Herein, we investigated the effect and mechanism of resveratrol function in PCa cell proliferation and migration and reported that TNF-receptor associated factor 6 (TRAF6), an unconventional E3 ligase, is a key mediator of resveratrol function to inhibit PCa cell growth and proliferation and targeted for lysosomal degradation by resveratrol. MTT and cell counting demonstrated that resveratrol inhibited the viability and proliferation in DU145 and PC3 cells. Resveratrol (50 μM) mediated the degradation of TRAF6 which in turn facilitated repression of the NF-κB pathway. Also, wound healing and transwell migration assays and level of EMT-related proteins showed that resveratrol used TRAF6, at least in part to inhibit cell migration. Overexpression of TRAF6 augmented EMT in PCa by upregulating the expression of transcription factor SLUG. Moreover, TRAF6 overexpression was closely associated with EMT process through the NF-κB pathway. Our exploration exhibited that resveratrol may inhibit EMT through the TRAF6/NF-κB/SLUG axis. Altogether, this study represents that TRAF6 acts as an intermediary of resveratrol action to suppress PCa cell proliferation and migration, and concerns future attention to obtain as a therapeutic target for the treatment of PCa.



中文翻译:

白藜芦醇诱导TRAF6耗竭并抑制前列腺癌细胞的增殖和迁移。

尽管前列腺癌(PCa)的早期诊断可提高5年生存率100%的预期寿命,但转移PCa是PCa死亡的根本原因,因此需要一种先进的靶向治疗策略。转移被认为是由上皮-间质转化(EMT)事件引发的,在该事件中,肿瘤细胞将其上皮特性改变为间充质形式,并加剧了癌症的进展。在本文中,我们研究了白藜芦醇功能在PCa细胞增殖和迁移中的作用和机制,并报道了非常规E3连接酶TNF受体相关因子6(TRAF6)是白藜芦醇抑制PCa细胞生长和增殖的关键介质。靶向白藜芦醇的溶酶体降解。MTT和细胞计数表明白藜芦醇抑制DU145和PC3细胞的活力和增殖。白藜芦醇(50μM)介导TRAF6的降解,进而促进了NF-κB通路的抑制。同样,伤口愈合和穿孔迁移分析以及与EMT相关的蛋白水平表明,白藜芦醇至少部分地使用TRAF6抑制细胞迁移。TRAF6的过表达通过上调转录因子SLUG的表达增强了PCa中的EMT。此外,TRAF6的过表达通过NF-κB途径与EMT过程密切相关。我们的研究表明,白藜芦醇可以通过TRAF6 /NF-κB/ SLUG轴抑制EMT。总而言之,这项研究表明TRAF6作为白藜芦醇作用的中介,可抑制PCa细胞的增殖和迁移,

更新日期:2019-11-09
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