相扑蛋白
脂肪酸合酶
污渍
基因沉默
泛素
癌细胞
化学
酶
生物化学
癌症研究
MTT法
癌症
生物
细胞生长
分子生物学
基因
遗传学
作者
Andrea Floris,Michael Mazarei,Xi Yang,Aaron Robinson,Jennifer Zhou,Antonio Barberis,Guy Droogmans,Emanuela Azara,Ylenia Spissu,Ainhoa Iglesias–Ara,Sandro Orrù,Maria Lauda Tomasi
出处
期刊:Biomolecules
[MDPI AG]
日期:2020-03-31
卷期号:10 (4): 529-529
被引量:22
摘要
Existing therapeutic strategies for breast cancer are limited by tumor recurrence and drug-resistance. Antioxidant plant-derived compounds such as flavonoids reduce adverse outcomes and have been identified as a potential source of antineoplastic agent with less undesirable side effects. Here, we describe the novel regulation of fatty-acid synthase (FASN), the key enzyme in de novo fatty-acid synthesis, whereby Vitis vinifera L. cv Vermentino leaf hydroalcoholic extract lowers its protein stability that is regulated by small ubiquitin-like modifier (SUMO)ylation. The phenolic compounds characterization was performed by liquid chromatography–mass spectrometry (LC–MS), whereas mass spectrometry (LC–MS/MS), Western blotting/co-immunoprecipitation (Co-IP) and RT-PCR, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), clonogenicity assays, and FACS analysis were used to measure the expression of targets and tumorigenicity. Vermentino extract exhibits antitumorigenic effects, and we went on to determine that FASN and ubiquitin-conjugating enzyme 9 (UBC9), the sole E2 enzyme required for SUMOylation, were significantly reduced. Moreover, FASN was found SUMOylated in human breast cancer tissues and cell lines, and lack of SUMOylation caused by SUMO2 silencing reduced FASN protein stability. These results suggest that SUMOylation protects FASN against proteasomal degradation and may exert oncogenic activity through alteration of lipid metabolism, whereas Vermentino extract inhibits these effects which supports the additional validation of the therapeutic value of this compound in breast cancer.
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