2. Academic Validation
  3. Aloe-emodin targets multiple signaling pathways by blocking ubiquitin-mediated degradation of DUSP1 in nasopharyngeal carcinoma cells

Aloe-emodin targets multiple signaling pathways by blocking ubiquitin-mediated degradation of DUSP1 in nasopharyngeal carcinoma cells

  • Phytother Res. 2023 Mar 3. doi: 10.1002/ptr.7793.
Shanlin Chen 1 2 3,  Xiaoxue Guan 2 4,  Lei Xie 1 3,  Chuanyu Liu 5,  Chunhong Li 6 7,  Min He 1,  Jiahua Hu 6,  Hui Fan 8,  Quanwen Li 9,  Liuping Xie 1 3,  Mingqing Yang 4,  Xiaoling Zhang 10,  Shengjun Xiao 2 4 11,  Jianhong Tang 1 3 7
Affiliations

Affiliations

  • 1 Department of Pharmacy, The Second Affiliated Hospital, Guilin Medical University, Guilin, China.
  • 2 Key Laboratory of Tumor Immunology and Microenvironmental Regulation, Guilin Medical University, Guilin, China.
  • 3 Guangxi Key Laboratory of Diabetic Systems Medicine, Guilin Medical University, Guilin, China.
  • 4 Department of Pathology, The Second Affiliated Hospital, Guilin Medical University, Guilin, China.
  • 5 Department of Pharmacy, The Affiliated Hospital of Guilin Medical University, Guilin, China.
  • 6 Central Laboratory, Guangxi Health Commission Key Laboratory of Glucose and Lipid Metabolism Disorders, The Second Affiliated Hospital of Guilin Medical University, Guilin, China.
  • 7 Guangxi Health Commission Key Laboratory of Glucose and Lipid Metabolism Disorders, The Second Affiliated Hospital of Guilin Medical University, Guilin, China.
  • 8 Department of Otolaryngology, The Second Affiliated Hospital, Guilin Medical University, Guilin, China.
  • 9 Department of Cardiology, The Affiliated Hospital of Guilin Medical University, Guilin, China.
  • 10 Department of Physiology, Faculty of Basic Medical Science, Guilin Medical University, Guilin, China.
  • 11 Guangxi Key Laboratory of Metabolic Diseases Research, No. 924 Hospital of PLA Joint Logistic Support Force, Guilin, China.
PMID: 36866539 DOI: 10.1002/ptr.7793
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.

Keywords

AKT signal pathway; Aloe-emodin; Dual specificity phosphatase 1; ERK signal pathway; Nasopharyngeal carcinoma; p38-MAPK signal pathway.

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