Aloe-emodin targets multiple signaling pathways by blocking ubiquitin-mediated degradation of DUSP1 in nasopharyngeal carcinoma cells
Shanlin Chen
Department of Pharmacy, The Second Affiliated Hospital, Guilin Medical University, Guilin, China
Key Laboratory of Tumor Immunology and Microenvironmental Regulation, Guilin Medical University, Guilin, China
Guangxi Key Laboratory of Diabetic Systems Medicine, Guilin Medical University, Guilin, China
Search for more papers by this authorXiaoxue Guan
Key Laboratory of Tumor Immunology and Microenvironmental Regulation, Guilin Medical University, Guilin, China
Department of Pathology, The Second Affiliated Hospital, Guilin Medical University, Guilin, China
Search for more papers by this authorLei Xie
Department of Pharmacy, The Second Affiliated Hospital, Guilin Medical University, Guilin, China
Guangxi Key Laboratory of Diabetic Systems Medicine, Guilin Medical University, Guilin, China
Search for more papers by this authorChuanyu Liu
Department of Pharmacy, The Affiliated Hospital of Guilin Medical University, Guilin, China
Search for more papers by this authorChunhong Li
Central Laboratory, Guangxi Health Commission Key Laboratory of Glucose and Lipid Metabolism Disorders, The Second Affiliated Hospital of Guilin Medical University, Guilin, China
Guangxi Health Commission Key Laboratory of Glucose and Lipid Metabolism Disorders, The Second Affiliated Hospital of Guilin Medical University, Guilin, China
Search for more papers by this authorMin He
Department of Pharmacy, The Second Affiliated Hospital, Guilin Medical University, Guilin, China
Search for more papers by this authorJiahua Hu
Central Laboratory, Guangxi Health Commission Key Laboratory of Glucose and Lipid Metabolism Disorders, The Second Affiliated Hospital of Guilin Medical University, Guilin, China
Search for more papers by this authorHui Fan
Department of Otolaryngology, The Second Affiliated Hospital, Guilin Medical University, Guilin, China
Search for more papers by this authorQuanwen Li
Department of Cardiology, The Affiliated Hospital of Guilin Medical University, Guilin, China
Search for more papers by this authorLiuping Xie
Department of Pharmacy, The Second Affiliated Hospital, Guilin Medical University, Guilin, China
Guangxi Key Laboratory of Diabetic Systems Medicine, Guilin Medical University, Guilin, China
Search for more papers by this authorMingqing Yang
Department of Pathology, The Second Affiliated Hospital, Guilin Medical University, Guilin, China
Search for more papers by this authorCorresponding Author
Xiaoling Zhang
Department of Physiology, Faculty of Basic Medical Science, Guilin Medical University, Guilin, China
Correspondence
Xiaoling Zhang, Department of Physiology, Faculty of Basic Medical Science, Guilin Medical University, Guilin, Guangxi 541199, China.
Email: [email protected]
Shengjun Xiao, Key Laboratory of Tumor Immunology and Microenvironmental Regulation, Guilin Medical University, Guilin, Guangxi 541199, China.
Email: [email protected]
Jianhong Tang, Department of Pharmacy, The Second Affiliated Hospital Guilin Medical University, Guilin, Guangxi 541199, China.
Email: [email protected]
Search for more papers by this authorCorresponding Author
Shengjun Xiao
Key Laboratory of Tumor Immunology and Microenvironmental Regulation, Guilin Medical University, Guilin, China
Department of Pathology, The Second Affiliated Hospital, Guilin Medical University, Guilin, China
Guangxi Key Laboratory of Metabolic Diseases Research, No. 924 Hospital of PLA Joint Logistic Support Force, Guilin, China
Correspondence
Xiaoling Zhang, Department of Physiology, Faculty of Basic Medical Science, Guilin Medical University, Guilin, Guangxi 541199, China.
Email: [email protected]
Shengjun Xiao, Key Laboratory of Tumor Immunology and Microenvironmental Regulation, Guilin Medical University, Guilin, Guangxi 541199, China.
Email: [email protected]
Jianhong Tang, Department of Pharmacy, The Second Affiliated Hospital Guilin Medical University, Guilin, Guangxi 541199, China.
Email: [email protected]
Search for more papers by this authorCorresponding Author
Jianhong Tang
Department of Pharmacy, The Second Affiliated Hospital, Guilin Medical University, Guilin, China
Guangxi Key Laboratory of Diabetic Systems Medicine, Guilin Medical University, Guilin, China
Guangxi Health Commission Key Laboratory of Glucose and Lipid Metabolism Disorders, The Second Affiliated Hospital of Guilin Medical University, Guilin, China
Correspondence
Xiaoling Zhang, Department of Physiology, Faculty of Basic Medical Science, Guilin Medical University, Guilin, Guangxi 541199, China.
Email: [email protected]
Shengjun Xiao, Key Laboratory of Tumor Immunology and Microenvironmental Regulation, Guilin Medical University, Guilin, Guangxi 541199, China.
Email: [email protected]
Jianhong Tang, Department of Pharmacy, The Second Affiliated Hospital Guilin Medical University, Guilin, Guangxi 541199, China.
Email: [email protected]
Search for more papers by this authorShanlin Chen
Department of Pharmacy, The Second Affiliated Hospital, Guilin Medical University, Guilin, China
Key Laboratory of Tumor Immunology and Microenvironmental Regulation, Guilin Medical University, Guilin, China
Guangxi Key Laboratory of Diabetic Systems Medicine, Guilin Medical University, Guilin, China
Search for more papers by this authorXiaoxue Guan
Key Laboratory of Tumor Immunology and Microenvironmental Regulation, Guilin Medical University, Guilin, China
Department of Pathology, The Second Affiliated Hospital, Guilin Medical University, Guilin, China
Search for more papers by this authorLei Xie
Department of Pharmacy, The Second Affiliated Hospital, Guilin Medical University, Guilin, China
Guangxi Key Laboratory of Diabetic Systems Medicine, Guilin Medical University, Guilin, China
Search for more papers by this authorChuanyu Liu
Department of Pharmacy, The Affiliated Hospital of Guilin Medical University, Guilin, China
Search for more papers by this authorChunhong Li
Central Laboratory, Guangxi Health Commission Key Laboratory of Glucose and Lipid Metabolism Disorders, The Second Affiliated Hospital of Guilin Medical University, Guilin, China
Guangxi Health Commission Key Laboratory of Glucose and Lipid Metabolism Disorders, The Second Affiliated Hospital of Guilin Medical University, Guilin, China
Search for more papers by this authorMin He
Department of Pharmacy, The Second Affiliated Hospital, Guilin Medical University, Guilin, China
Search for more papers by this authorJiahua Hu
Central Laboratory, Guangxi Health Commission Key Laboratory of Glucose and Lipid Metabolism Disorders, The Second Affiliated Hospital of Guilin Medical University, Guilin, China
Search for more papers by this authorHui Fan
Department of Otolaryngology, The Second Affiliated Hospital, Guilin Medical University, Guilin, China
Search for more papers by this authorQuanwen Li
Department of Cardiology, The Affiliated Hospital of Guilin Medical University, Guilin, China
Search for more papers by this authorLiuping Xie
Department of Pharmacy, The Second Affiliated Hospital, Guilin Medical University, Guilin, China
Guangxi Key Laboratory of Diabetic Systems Medicine, Guilin Medical University, Guilin, China
Search for more papers by this authorMingqing Yang
Department of Pathology, The Second Affiliated Hospital, Guilin Medical University, Guilin, China
Search for more papers by this authorCorresponding Author
Xiaoling Zhang
Department of Physiology, Faculty of Basic Medical Science, Guilin Medical University, Guilin, China
Correspondence
Xiaoling Zhang, Department of Physiology, Faculty of Basic Medical Science, Guilin Medical University, Guilin, Guangxi 541199, China.
Email: [email protected]
Shengjun Xiao, Key Laboratory of Tumor Immunology and Microenvironmental Regulation, Guilin Medical University, Guilin, Guangxi 541199, China.
Email: [email protected]
Jianhong Tang, Department of Pharmacy, The Second Affiliated Hospital Guilin Medical University, Guilin, Guangxi 541199, China.
Email: [email protected]
Search for more papers by this authorCorresponding Author
Shengjun Xiao
Key Laboratory of Tumor Immunology and Microenvironmental Regulation, Guilin Medical University, Guilin, China
Department of Pathology, The Second Affiliated Hospital, Guilin Medical University, Guilin, China
Guangxi Key Laboratory of Metabolic Diseases Research, No. 924 Hospital of PLA Joint Logistic Support Force, Guilin, China
Correspondence
Xiaoling Zhang, Department of Physiology, Faculty of Basic Medical Science, Guilin Medical University, Guilin, Guangxi 541199, China.
Email: [email protected]
Shengjun Xiao, Key Laboratory of Tumor Immunology and Microenvironmental Regulation, Guilin Medical University, Guilin, Guangxi 541199, China.
Email: [email protected]
Jianhong Tang, Department of Pharmacy, The Second Affiliated Hospital Guilin Medical University, Guilin, Guangxi 541199, China.
Email: [email protected]
Search for more papers by this authorCorresponding Author
Jianhong Tang
Department of Pharmacy, The Second Affiliated Hospital, Guilin Medical University, Guilin, China
Guangxi Key Laboratory of Diabetic Systems Medicine, Guilin Medical University, Guilin, China
Guangxi Health Commission Key Laboratory of Glucose and Lipid Metabolism Disorders, The Second Affiliated Hospital of Guilin Medical University, Guilin, China
Correspondence
Xiaoling Zhang, Department of Physiology, Faculty of Basic Medical Science, Guilin Medical University, Guilin, Guangxi 541199, China.
Email: [email protected]
Shengjun Xiao, Key Laboratory of Tumor Immunology and Microenvironmental Regulation, Guilin Medical University, Guilin, Guangxi 541199, China.
Email: [email protected]
Jianhong Tang, Department of Pharmacy, The Second Affiliated Hospital Guilin Medical University, Guilin, Guangxi 541199, China.
Email: [email protected]
Search for more papers by this authorShanlin Chen, Xiaoxue Guan and Lei Xie are contributed equally to this work.
Abstract
Aloe-emodin (AE) has been shown to inhibit the proliferation of several cancer cell lines, including human nasopharyngeal carcinoma (NPC) cell lines. In this study, we confirmed that AE inhibited malignant biological behaviors, including cell viability, abnormal proliferation, apoptosis, and migration of NPC cells. Western blotting analysis revealed that AE upregulated the expression of DUSP1, an endogenous inhibitor of multiple cancer-associated signaling pathways, resulting in blockage of the extracellular signal-regulated kinase (ERK)-1/2, protein kinase B (AKT), and p38-mitogen activated protein kinase（p38-MAPK） signaling pathways in NPC cell lines. Moreover, the selective inhibitor of DUSP1, BCI-hydrochloride, partially reversed the AE-induced cytotoxicity and blocked the aforementioned signaling pathways in NPC cells. In addition, the binding between AE and DUSP1 was predicted via molecular docking analysis using AutoDock-Vina software and further verified via a microscale thermophoresis assay. The binding amino acid residues were adjacent to the predicted ubiquitination site (Lys192) of DUSP1. Immunoprecipitation with the ubiquitin antibody, ubiquitinated DUSP1 was shown to be upregulated by AE. Our findings revealed that AE can stabilize DUSP1 by blocking its ubiquitin–proteasome-mediated degradation and proposed an underlying mechanism by which AE-upregulated DUSP1 may potentially target multiple pathways in NPC cells.
CONFLICT OF INTEREST
The authors declare no conflicts of interest.
Open Research
DATA AVAILABILITY STATEMENT
All data generated/analyzed in this study are available on request from the authors.
Supporting Information
| Filename | Description |
|---|---|
| ptr7793-sup-0001-TableS1.xlsxExcel 2007 spreadsheet , 10.7 KB | Table S1. Supporting information. |
| ptr7793-sup-0002-FigureS1.pdfPDF document, 3 MB | Figure S1. Western blot Figure 3. |
| ptr7793-sup-0003-FigureS2.pdfPDF document, 2.3 MB | Figure S2. Western blot Figure 4. |
| ptr7793-sup-0004-FigureS3.pdfPDF document, 1.5 MB | Figure S3. Western blot Figure 8. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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