The Inhibitory Effect of 6-Gingerol on Ubiquitin-Specific Peptidase 14 Enhances Autophagy-Dependent Ferroptosis and Anti-Tumor in vivo and in vitro.
The Inhibitory Effect of 6-Gingerol on Ubiquitin-Specific Peptidase 14 Enhances Autophagy-Dependent Ferroptosis and Anti-Tumor in vivo and in vitro.
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DOI：
10.3389/fphar.2020.598555
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发表时间：
2020
影响因子：
5.6
通讯作者：
Sun Z
中科院分区：
文献类型：
--
作者：
Tsai Y;Xia C;Sun Z
肺癌是最常见的恶性肿瘤，是全球癌症相关死亡的主要原因。从草药中提取生物活性物质被认为是传统治疗的替代方法。6-姜酚是一种天然存在的苯酚，存在于生姜中，可用于治疗肿瘤和抑制炎症。确定6-姜酚是否可用作肿瘤治疗剂。在本研究中，荷瘤小鼠被用作动物模型，A549被用作细胞模型。Western blot检测自噬相关蛋白泛素特异性肽酶14（USP 14）、Beclin 1、微管相关蛋白轻链3（LC 3）和铁凋亡相关蛋白核受体辅激活子4（NCOA 4）、铁蛋白重链1（FTH 1）、转铁蛋白受体1（TfR 1）、谷胱甘肽过氧化物酶4（GPX 4）的表达，转录激活因子4（ATF4）。MTT法和EdU法检测A549细胞活力。用H & E和免疫荧光法对蛋白质的表达进行定位和检测。使用荧光探针进行活性氧的检测。结果发现，6-姜酚的给药降低了USP 14的表达，大大增加了自噬体的数量、活性氧（ROS）和铁浓度，降低了A549细胞的存活率和增殖率，并显著降低了肿瘤体积和重量。结果表明，6-姜酚通过抑制USP14表达及其下游调节自噬依赖性铁凋亡来抑制肺癌细胞生长，揭示了6-姜酚作为治疗化合物在A549中的功能和功效及其可能的作用机制。
Lung cancer is the most common malignant tumor and is the leading cause of cancer-related deaths worldwide. Extraction of bioactive substances from herbs is considered as an alternative method to traditional treatment. 6-Gingerol is a naturally occurring phenol found in ginger that can be used to treat tumors and suppress inflammation. To determine whether 6-Gingerol can be used as a therapeutic agent for tumors. In this study, tumor-bearing mice were used as an animal model and A549 as a cell model. Western blot was used to detect the expression of autophagy related proteins ubiquitin-specific peptidase 14 (USP14), Beclin1, microtubule-associated protein light chain 3 (LC3) and ferroptosis related proteins nuclear receptor coactivator 4 (NCOA4), ferritin heavy chain 1 (FTH1), transferrin receptor 1 (TfR1), glutathione peroxidase 4 (GPX4), activating transcription factor4 (ATF4) in vivo and in vitro. MTT and EdU were used to detect the viability of A549 cells. H&E and immunofluorescence were used to localize and detect the expression of proteins. The detection of reactive oxygen species was performed using fluorescence probes. It was found that the administration of 6-Gingerol decreased the expression of USP14, greatly increased the number of autophagosomes, reactive oxygen species (ROS) and iron concentration, decreased the survival and proliferation rate of A549 cells, and significantly decreased tumor volume and weight. The results indicate that 6-Gingerol inhibits lung cancer cell growth via suppression of USP14 expression and its downstream regulation of autophagy-dependent ferroptosis, revealing the function and efficacy of 6-Gingerol as a therapeutic compound in A549 and its possible mechanism of action.
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影响因子：
5.3
作者：
Tripathi R;Ash D;Shaha C
通讯作者：
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影响因子：
3.8
作者：
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通讯作者：
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影响因子：
64.5
作者：
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通讯作者：
Yuan J
影响因子：
64.8
作者：
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通讯作者：
Kimmelman, Alec C.
影响因子：
254.7
作者：
Siegel, Rebecca;Ma, Jiemin;Jemal, Ahmedin
通讯作者：
Jemal, Ahmedin