2. Academic Validation
  3. Therapeutic potential of targeting MKK3-p38 axis with Capsaicin for Nasopharyngeal Carcinoma

Therapeutic potential of targeting MKK3-p38 axis with Capsaicin for Nasopharyngeal Carcinoma

  • Theranostics. 2020 Jun 24;10(17):7906-7920. doi: 10.7150/thno.45191.
Chengyao Chiang 1,  Min Zhang 1,  Dian Wang 2,  Tian Xiao 1,  Lizhi Zhu 3,  Kai Chen 4,  Junrong Huang 3,  Jingying Huang 1,  Jiang Zhu 1,  Li Li 1,  Cheng Chen 1,  Yangchao Chen 5,  Hongyi Hu 6,  Wenqi Jiang 7,  Yongdong Zou 1,  Ting Wang 2 8,  Duo Zheng 1
Affiliations

Affiliations

  • 1 Guangdong Provincial Key Laboratory of Regional Immunity and Diseases, Shenzhen University International Cancer Center, Department of Cell Biology and Genetics, School of Medicine, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen 518055, China.
  • 2 Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, 410013, China.
  • 3 Institute of Translation Medicine, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen, 518035, China.
  • 4 School of Materials Science and Engineering, Central South University of Forestry and Technology, Changsha, 410004, China.
  • 5 School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, NT, Hong Kong.
  • 6 Department of Otolaryngology, Peking University Shenzhen Hospital, Shenzhen, 518036, China.
  • 7 Sun Yet-sen University Cancer Center, Guangzhou, China.
  • 8 Guangzhou Henvcom Bioscience Co Ltd, Guangzhou, 510535, China.
PMID: 32685028 DOI: 10.7150/thno.45191
Abstract

Background: Capsaicin is an active compound found in Plants of the Capsicum genus; it has a range of therapeutic benefits, including anti-tumor effects. Here we aimed to delineate the inhibitory effects of capsaicin on nasopharyngeal carcinoma (NPC). Methods: The anti-cancer effects of capsaicin were confirmed in NPC cell lines and xenograft mouse models, using CCK-8, clonogenic, wound-healing, transwell migration and invasion assays. Co-immunoprecipitation, western blotting and pull-down assays were used to determine the effects of capsaicin on the MKK3-p38 axis. Cell proliferation and EMT marker expression were monitored in MKK3 knockdown (KD) or over-expression NPC cell lines treated with or without capsaicin. Finally, immunohistochemistry was performed on NPC specimens from NPC patients (n = 132) and the clinical relevance was analyzed. Results: Capsaicin inhibited cell proliferation, mobility and promoted Apoptosis in NPC cells. Then we found that capsaicin directly targets p38 for dephosphorylation. As such, MKK3-induced p38 activation was inhibited by capsaicin. Furthermore, we found that capsaicin-induced inhibition of cell motility was mediated by fucokinase. Xenograft models demonstrated the inhibitory effects of capsaicin treatment on NPC tumor growth in vivo, and analysis of clinical NPC samples confirmed that MKK3 phosphorylation was associated with NPC tumor growth and lymphoid node metastasis. Conclusions: The MKK3-p38 axis represents a potential therapeutic target for capsaicin. MKK3 phosphorylation might serve as a biomarker to identify NPC patients most likely to benefit from adjunctive capsaicin treatment.

Keywords

Capsaicin; FUK; MKK3-p38; cell mobility; nasopharyngeal carcinoma.

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