PMID- 32349518
OWN - NLM
STAT- MEDLINE
DCOM- 20200827
LR  - 20211204
IS  - 1793-6853 (Electronic)
IS  - 0192-415X (Linking)
VI  - 48
IP  - 3
DP  - 2020
TI  - Cinobufagin Triggers Defects in Spindle Formation and Cap-Dependent Translation 
      in Liver Cancer Cells by Inhibiting the AURKA-mTOR-eIF4E Axis.
PG  - 651-678
LID - 10.1142/S0192415X20500330 [doi]
AB  - Cinobufagin is a Na(+)/K(+)-ATPase (NKA) inhibitor with excellent anticancer 
      effects to prolong the survival of patients. The purpose of the present study was 
      to clarify the underlying mechanism of the anticancer effects of cinobufagin 
      using overexpression or inhibition of aurora kinase A (AURKA) signaling. First, 
      high expression of Na(+)/K(+)-ATPase alpha 1 subunit (ATP1A1) and AURAK resulted 
      in increased malignant transformation in hepatocellular carcinoma (HCC) patients 
      using the cancer genome atlas (TCGA) data and tissue samples. After treatment 
      with cinobufagin, we successfully screened 202, 249, and 335 changing expression 
      proteins in Huh-7 cells under normal, overexpression, and inhibition of AURKA 
      using tandem mass tags (TMT)-labeled quantitative proteomics coupled to 2D liquid 
      chromatography-tandem mass spectrometry (LC-MS/MS). Bioinformatics analysis 
      revealed that these molecules were closely associated with chromosome 
      segregation, DNA damage, and regulation of translation processes. We further 
      confirmed that cinobufagin induced DNA damage and chromosome segregation 
      disorders and suppresses translational processing in oncogenes by decreasing the 
      expression of AURKA, mechanistic target of rapamycin kinase (mTOR), p-mTOR, 
      p-extracellular regulated protein kinases (ERK), eukaryotic translation 
      initiation factor 4E (eIF4E), and p-eIF4E, while increasing the expression of 
      p-eukaryotic translation initiation factor 4E binding protein 1 (4E-BP1) (S65, 
      T37, T46, T45) and increasing the interaction between eIF4 and 4E-BP1. Our 
      results suggested that cinobufagin performed an antitumor effects in liver cancer 
      cells by inhibiting the AURKA-mTOR-eIF4E axis.
FAU - Jin, Xiaohan
AU  - Jin X
AD  - Central Laboratory, Logistics University of Chinese People's Armed Police Force, 
      Tianjin City 300309, P. R. China.
FAU - Wang, Jiabao
AU  - Wang J
AD  - Central Laboratory, Logistics University of Chinese People's Armed Police Force, 
      Tianjin City 300309, P. R. China.
FAU - Zou, Shuang
AU  - Zou S
AD  - Central Laboratory, Logistics University of Chinese People's Armed Police Force, 
      Tianjin City 300309, P. R. China.
FAU - Xu, Ruicheng
AU  - Xu R
AD  - Central Laboratory, Logistics University of Chinese People's Armed Police Force, 
      Tianjin City 300309, P. R. China.
FAU - Cao, Jin
AU  - Cao J
AD  - Department of Gastroenterology and Hepatology, Third Central Hospital of Tianjin, 
      Tianjin City 300170, P. R. China.
FAU - Zhang, Yan
AU  - Zhang Y
AD  - Central Laboratory, Logistics University of Chinese People's Armed Police Force, 
      Tianjin City 300309, P. R. China.
FAU - Guo, Jia
AU  - Guo J
AD  - Central Laboratory, Logistics University of Chinese People's Armed Police Force, 
      Tianjin City 300309, P. R. China.
FAU - Wen, Xiaochang
AU  - Wen X
AD  - Central Laboratory, Logistics University of Chinese People's Armed Police Force, 
      Tianjin City 300309, P. R. China.
FAU - Deng, Sanmin
AU  - Deng S
AD  - Central Laboratory, Logistics University of Chinese People's Armed Police Force, 
      Tianjin City 300309, P. R. China.
FAU - Zheng, Yupiao
AU  - Zheng Y
AD  - Department of Gastroenterology and Hepatology, Third Central Hospital of Tianjin, 
      Tianjin City 300170, P. R. China.
FAU - Zhu, Yu
AU  - Zhu Y
AD  - Department of Clinical Laboratory, Tianjin Key Laboratory of Cerebral Vessels and 
      Neurodegenerative Diseases, Tianjin Huanhu Hospital, Tianjin City 300350, P. R. 
      China.
FAU - Wang, Fengmei
AU  - Wang F
AD  - Department of Gastroenterology and Hepatology, Third Central Hospital of Tianjin, 
      Tianjin City 300170, P. R. China.
FAU - Xu, Zhongwei
AU  - Xu Z
AD  - Central Laboratory, Logistics University of Chinese People's Armed Police Force, 
      Tianjin City 300309, P. R. China.
LA  - eng
PT  - Journal Article
DEP - 20200430
PL  - Singapore
TA  - Am J Chin Med
JT  - The American journal of Chinese medicine
JID - 7901431
RN  - 0 (Antineoplastic Agents, Phytogenic)
RN  - 0 (Bufanolides)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (ELF4 protein, human)
RN  - 0 (Transcription Factors)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (AURKA protein, human)
RN  - EC 2.7.11.1 (Aurora Kinase A)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 3.6.1.- (ATP1A1 protein, human)
RN  - EC 7.2.2.13 (Sodium-Potassium-Exchanging ATPase)
RN  - T9PSN4R8IR (cinobufagin)
SB  - IM
MH  - *Antineoplastic Agents, Phytogenic
MH  - Aurora Kinase A/*metabolism
MH  - Bufanolides/*pharmacology
MH  - Carcinoma, Hepatocellular/*genetics/*metabolism
MH  - Chromosome Segregation/drug effects
MH  - DNA Damage/drug effects
MH  - DNA-Binding Proteins/*metabolism
MH  - Gene Expression/drug effects
MH  - Liver Neoplasms/*genetics/*metabolism
MH  - Oncogenes/genetics
MH  - Protein Biosynthesis/*drug effects
MH  - Sodium-Potassium-Exchanging ATPase/metabolism
MH  - TOR Serine-Threonine Kinases/*metabolism
MH  - Transcription Factors/*metabolism
MH  - Tumor Cells, Cultured
OTO - NOTNLM
OT  - Aurora Kinase A
OT  - Cap-Dependent Translation
OT  - Cinobufagin
OT  - Hepatoma
OT  - Spindle Formation
EDAT- 2020/05/01 06:00
MHDA- 2020/08/28 06:00
CRDT- 2020/05/01 06:00
PHST- 2020/05/01 06:00 [pubmed]
PHST- 2020/08/28 06:00 [medline]
PHST- 2020/05/01 06:00 [entrez]
AID - 10.1142/S0192415X20500330 [doi]
PST - ppublish
SO  - Am J Chin Med. 2020;48(3):651-678. doi: 10.1142/S0192415X20500330. Epub 2020 Apr 
      30.