PMID- 32685028
OWN - NLM
STAT- MEDLINE
DCOM- 20210503
LR  - 20210503
IS  - 1838-7640 (Electronic)
IS  - 1838-7640 (Linking)
VI  - 10
IP  - 17
DP  - 2020
TI  - Therapeutic potential of targeting MKK3-p38 axis with Capsaicin for 
      Nasopharyngeal Carcinoma.
PG  - 7906-7920
LID - 10.7150/thno.45191 [doi]
AB  - 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.
CI  - (c) The author(s).
FAU - Chiang, Chengyao
AU  - Chiang C
AD  - 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.
FAU - Zhang, Min
AU  - Zhang M
AD  - 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.
FAU - Wang, Dian
AU  - Wang D
AD  - Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, 
      410013, China.
FAU - Xiao, Tian
AU  - Xiao T
AD  - 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.
FAU - Zhu, Lizhi
AU  - Zhu L
AD  - Institute of Translation Medicine, Shenzhen Second People's Hospital, The First 
      Affiliated Hospital of Shenzhen University, Shenzhen, 518035, China.
FAU - Chen, Kai
AU  - Chen K
AD  - School of Materials Science and Engineering, Central South University of Forestry 
      and Technology, Changsha, 410004, China.
FAU - Huang, Junrong
AU  - Huang J
AD  - Institute of Translation Medicine, Shenzhen Second People's Hospital, The First 
      Affiliated Hospital of Shenzhen University, Shenzhen, 518035, China.
FAU - Huang, Jingying
AU  - Huang J
AD  - 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.
FAU - Zhu, Jiang
AU  - Zhu J
AD  - 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.
FAU - Li, Li
AU  - Li L
AD  - 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.
FAU - Chen, Cheng
AU  - Chen C
AD  - 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.
FAU - Chen, Yangchao
AU  - Chen Y
AD  - School of Biomedical Sciences, Faculty of Medicine, The Chinese University of 
      Hong Kong, Shatin, NT, Hong Kong.
FAU - Hu, Hongyi
AU  - Hu H
AD  - Department of Otolaryngology, Peking University Shenzhen Hospital, Shenzhen, 
      518036, China.
FAU - Jiang, Wenqi
AU  - Jiang W
AD  - Sun Yet-sen University Cancer Center, Guangzhou, China.
FAU - Zou, Yongdong
AU  - Zou Y
AD  - 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.
FAU - Wang, Ting
AU  - Wang T
AD  - Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, 
      410013, China.
AD  - Guangzhou Henvcom Bioscience Co Ltd, Guangzhou, 510535, China.
FAU - Zheng, Duo
AU  - Zheng D
AD  - 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.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200624
PL  - Australia
TA  - Theranostics
JT  - Theranostics
JID - 101552395
RN  - EC 2.7.1.- (Phosphotransferases (Alcohol Group Acceptor))
RN  - EC 2.7.1.52 (fucokinase)
RN  - EC 2.7.12.2 (MAP Kinase Kinase 3)
RN  - EC 2.7.12.2 (MAP2K3 protein, human)
RN  - S07O44R1ZM (Capsaicin)
SB  - IM
MH  - Animals
MH  - Capsaicin/*pharmacology/therapeutic use
MH  - Cell Line, Tumor
MH  - Cell Movement/drug effects
MH  - Cell Proliferation/drug effects
MH  - Epithelial-Mesenchymal Transition/drug effects
MH  - Female
MH  - Gene Knockdown Techniques
MH  - HEK293 Cells
MH  - Humans
MH  - MAP Kinase Kinase 3/genetics/*metabolism
MH  - MAP Kinase Signaling System/*drug effects/genetics
MH  - Male
MH  - Mice
MH  - Middle Aged
MH  - Nasopharyngeal Carcinoma/*drug therapy/pathology
MH  - Nasopharyngeal Neoplasms/*drug therapy/pathology
MH  - Neoplasm Invasiveness/pathology/prevention & control
MH  - Phosphorylation/drug effects
MH  - Phosphotransferases (Alcohol Group Acceptor)/genetics/metabolism
MH  - Xenograft Model Antitumor Assays
PMC - PMC7359099
OTO - NOTNLM
OT  - Capsaicin
OT  - FUK
OT  - MKK3-p38
OT  - cell mobility
OT  - nasopharyngeal carcinoma
COIS- Competing Interests: The authors have declared that no competing interest exists.
EDAT- 2020/07/21 06:00
MHDA- 2021/05/04 06:00
PMCR- 2020/01/01
CRDT- 2020/07/21 06:00
PHST- 2020/02/22 00:00 [received]
PHST- 2020/06/10 00:00 [accepted]
PHST- 2020/07/21 06:00 [entrez]
PHST- 2020/07/21 06:00 [pubmed]
PHST- 2021/05/04 06:00 [medline]
PHST- 2020/01/01 00:00 [pmc-release]
AID - thnov10p7906 [pii]
AID - 10.7150/thno.45191 [doi]
PST - epublish
SO  - Theranostics. 2020 Jun 24;10(17):7906-7920. doi: 10.7150/thno.45191. eCollection 
      2020.