SWATH proteomic profiling of prostate cancer cells identifies NUSAP1 as a potential molecular target for Galiellalactone

被引:15
|
作者
Garrido-Rodriguez, Martin [1 ,2 ,3 ]
Ortea, Ignacio [1 ,3 ]
Calzado, Marco A. [1 ,2 ,3 ]
Munoz, Eduardo [1 ,2 ,3 ]
Garcia, Victor [1 ,3 ]
机构
[1] Inst Maimonides Invest Biomed Cordoba IMIBIC, Cordoba, Spain
[2] Univ Cordoba, Dept Biol & Celular Fisiol & Immunol, Cordoba, Spain
[3] Hosp Univ Reina Sofia, Cordoba, Spain
关键词
Galiellalactone; Cell cycle; Prostate cancer; SWATH; NUSAP1; Confluence-dependent resistance; NF-KAPPA-B; CONFLUENCE-DEPENDENT RESISTANCE; ANDROGEN DEPRIVATION; CYCLE ARREST; CONSTITUTIVE ACTIVATION; TRANSCRIPTION FACTOR; STAT3; INHIBITION; EXPRESSION; APOPTOSIS;
D O I
10.1016/j.jprot.2018.10.012
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
Galiellalactone (GL) is a fungal metabolite that presents antitumor and antiinflammatory activities in vitro and in vivo. Previous studies have shown that GL targets NF-kappa B and STAT3 pathways and induces G(2)/M cell cycle arrest in androgen-insensitive prostate cancer cells. In this study, we show that GL-induced cell cycle arrest is independent of the NF-KB and STAT3 pathways in DU145 and PC-3 cells, and also that GL did not affect cell cycling in androgen-sensitive prostate cancer cells such as LNCaP and 22Rv1 cells. In addition, we showed confluence resistance to GL in DU145 cells. Using a SWATH proteomic approach we identified a down-regulation of Nucleolar and spindle associated protein 1 (NUSAP1) under DU145 confluence. Moreover the expression of NUSAP1 in LNCaP cells is low compared to DU145 cells. The inhibition of NUSAP1 by siRNAs induced resistance to GL in DU145 cells, suggesting that NUSAP1 may be a target for GL and could be useful as a biomarker for the responsiveness of the antitumor activity of GL. Altogether, our finding shed light to the potential of GL to be developed as a novel treatment of castration resistance prostate cancer.
引用
收藏
页码:217 / 229
页数:13
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