PMID- 29344654
OWN - NLM
STAT- MEDLINE
DCOM- 20180815
LR  - 20240223
IS  - 1791-3004 (Electronic)
IS  - 1791-2997 (Print)
IS  - 1791-2997 (Linking)
VI  - 17
IP  - 3
DP  - 2018 Mar
TI  - Tunicamycin inhibits colon carcinoma growth and aggressiveness via modulation of 
      the ERK-JNK-mediated AKT/mTOR signaling pathway.
PG  - 4203-4212
LID - 10.3892/mmr.2018.8444 [doi]
AB  - Epidemiology and evidence have demonstrated that colon carcinoma is one of the 
      most common gastrointestinal tumors in the clinic. Reports have suggested that 
      Tunicamycin significantly inhibits aggressiveness of colon carcinoma cells by 
      promotion of apoptosis. In the present study, the inhibitory effect of 
      tunicamycin on colon cancer cells and the potential underlying molecular 
      mechanism was investigated. Western blotting, immunohistochemistry, apoptotic 
      assays and immunofluorescence were used to analyze the therapeutic effects of 
      tunicamycin on apoptosis, growth, aggressiveness and cell cycle of colon tumor 
      cells, by downregulation of fibronectin, vimentin and E‑cadherin expression 
      levels. In vitro experiments demonstrated that tunicamycin significantly 
      inhibited growth, migration and invasion of colon carcinoma cells. In addition, 
      tunicamycin administration promoted apoptosis of colon carcinoma cells via 
      upregulation of apoptotic protease activating factor 1 and cytochrome c 
      expression levels, which are proteins that have a role in mitochondrial apoptosis 
      signaling. Cell cycle assays revealed that tunicamycin suppressed proliferation 
      and arrested S phase entry of colon carcinoma cells. Mechanistic analysis 
      demonstrated that tunicamycin reduced expression and phosphorylation levels of 
      extracellular signal‑regulated kinase (ERK), c‑JUN N‑terminal kinase (JNK) and 
      protein kinase B (AKT), and inhibited mammalian target of rapamycin (mTOR) 
      expression levels in colon carcinoma cells. Endogenous overexpression of ERK 
      inhibited tunicamycin‑mediated downregulation of JNK, AKT and mTOR expression, 
      which further blocked tunicamycin‑mediated inhibition of growth and 
      aggressiveness of colon carcinoma. In vivo assays revealed that tunicamycin 
      treatment significantly inhibited tumor growth and promoted apoptosis, which led 
      to long‑term survival of tumor‑bearing mice compared with the control group. In 
      conclusion, these results suggested that tunicamycin may inhibit growth and 
      aggressiveness of colon cancer via the ERK‑JNK‑mediated AKT/mTOR signaling 
      pathway, and suggested that tunicamycin may be a potential anti‑cancer agent for 
      colon carcinoma therapy.
FAU - You, Shuping
AU  - You S
AD  - Department of Anus and Bowel Surgery, Jingmen No. 2 People's Hospital, Jingmen, 
      Hubei 448000, P.R. China.
FAU - Li, Weihong
AU  - Li W
AD  - Department of Anus and Bowel Surgery, Jingmen No. 2 People's Hospital, Jingmen, 
      Hubei 448000, P.R. China.
FAU - Guan, Yun
AU  - Guan Y
AD  - Department of Anus and Bowel Surgery, Jingmen No. 2 People's Hospital, Jingmen, 
      Hubei 448000, P.R. China.
LA  - eng
PT  - Journal Article
PT  - Retracted Publication
DEP - 20180117
PL  - Greece
TA  - Mol Med Rep
JT  - Molecular medicine reports
JID - 101475259
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Cadherins)
RN  - 0 (Fibronectins)
RN  - 0 (Receptor, PAR-1)
RN  - 0 (Vimentin)
RN  - 11089-65-9 (Tunicamycin)
RN  - 9007-43-6 (Cytochromes c)
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.24 (Mapk1 protein, mouse)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
RN  - EC 2.7.12.2 (MAP Kinase Kinase 4)
SB  - IM
RIN - Mol Med Rep. 2024 Apr;29(4):. PMID: 38391013
MH  - Animals
MH  - Antineoplastic Agents/*pharmacology
MH  - Apoptosis/drug effects
MH  - Cadherins/genetics/metabolism
MH  - Cell Line, Tumor
MH  - Colonic Neoplasms/*drug therapy/genetics/metabolism/pathology
MH  - Cytochromes c/genetics/metabolism
MH  - Fibronectins/genetics/metabolism
MH  - *Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - MAP Kinase Kinase 4/genetics/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Nude
MH  - Mitogen-Activated Protein Kinase 1/antagonists & inhibitors/*genetics/metabolism
MH  - Mitogen-Activated Protein Kinase 3/antagonists & inhibitors/*genetics/metabolism
MH  - Neoplasm Invasiveness
MH  - Proto-Oncogene Proteins c-akt/genetics/metabolism
MH  - Receptor, PAR-1/genetics/metabolism
MH  - Signal Transduction
MH  - Survival Analysis
MH  - TOR Serine-Threonine Kinases/genetics/metabolism
MH  - Tumor Burden/drug effects
MH  - Tunicamycin/*pharmacology
MH  - Vimentin/genetics/metabolism
MH  - Xenograft Model Antitumor Assays
PMC - PMC5802191
OTO - NOTNLM
OT  - tunicamycin
OT  - colon carcinoma
OT  - apoptosis
OT  - aggressiveness
OT  - extracellular signal-regulated kinase/c-JUN N-terminal kinase
OT  - Akt/mechanistic target of rapamycin
EDAT- 2018/01/19 06:00
MHDA- 2018/08/16 06:00
PMCR- 2018/01/17
CRDT- 2018/01/19 06:00
PHST- 2016/11/13 00:00 [received]
PHST- 2017/07/05 00:00 [accepted]
PHST- 2018/01/19 06:00 [pubmed]
PHST- 2018/08/16 06:00 [medline]
PHST- 2018/01/19 06:00 [entrez]
PHST- 2018/01/17 00:00 [pmc-release]
AID - mmr-17-03-4203 [pii]
AID - 10.3892/mmr.2018.8444 [doi]
PST - ppublish
SO  - Mol Med Rep. 2018 Mar;17(3):4203-4212. doi: 10.3892/mmr.2018.8444. Epub 2018 Jan 
      17.