PMID- 29575026
OWN - NLM
STAT- MEDLINE
DCOM- 20190508
LR  - 20220321
IS  - 1097-4644 (Electronic)
IS  - 0730-2312 (Linking)
VI  - 119
IP  - 7
DP  - 2018 Jul
TI  - AG-1031 induced autophagic cell death and apoptosis in C6 glioma cells associated 
      with Notch-1 signaling pathway.
PG  - 5893-5903
LID - 10.1002/jcb.26781 [doi]
AB  - Glioma is the most common primary brain tumor with high morbidity and poor 
      prognosis. The effect of AG-1031, which is developed as an antineoplastic drug, 
      on C6 glioma cells is still not clear. The aim of this research was to explore 
      the effect of AG-1031 on C6 cells, and tried to find out its potential mechanism 
      on cytotoxicity of C6 cells. The 3-(4,5-dimethylthiazol -2-yl) -2,5- 
      diphenyltetrazolium bromide (MTT) assay showed that AG-1031 inhibited cell 
      viability in a concentration-dependent manner, whereas 3-methyadenine (3-MA) 
      reduced this effect. Results from hoechst 33342 staining and Western blot assay 
      indicated that AG-1031 induced C6 cell apoptosis. Western blot assay presented 
      that AG-1031 notably increased the LC3-II/LC3-I ratio and decreased the 
      expression of P62. Besides, our results showed that bafilomycin A1 increased the 
      expression of LC3-II in cells treated with AG-1031, which indicated that AG-1031 
      can increase autophagy in C6 cells. Meanwhile, Western blot assay showed that 
      AG-1031 can inhibit Notch-1 signaling by testing relative protein expressions. 
      The expression of the intracellular domain of Notch (NICD) also decreased 
      according to immunofluorescence assay. Additionally, the activation of Notch-1 
      signaling alleviated AG-1031-induced autophagic cell death and apoptosis. 
      Furthermore, phosphorylated Akt and its downstream effector mechanistic target of 
      rapamycin (mTOR) were reduced with AG-1031. These results suggest that AG-1031 
      may induce autophagic cell death through the inhibition of Akt-mTOR signaling 
      pathway by down-regulating Notch-1 signaling pathway and activating apoptosis in 
      C6 cells via Notch-1 signaling, which develops a new target spot to treat glioma 
      in the future.
CI  - (c) 2018 Wiley Periodicals, Inc.
FAU - Wang, Yan
AU  - Wang Y
AD  - Medical School, State Key Laboratory of Medicinal Chemical Biology, Key 
      Laboratory of Bioactive Materials for Ministry of Education, Nankai University, 
      Tianjin, China.
FAU - Wang, Hui
AU  - Wang H
AD  - College of Life Sciences, Nankai University, Tianjin, China.
FAU - Ge, Hui
AU  - Ge H
AD  - AscentGene, Inc., Gaithersburg, MD.
FAU - Yang, Zhuo
AU  - Yang Z
AUID- ORCID: 0000-0001-5212-0053
AD  - Medical School, State Key Laboratory of Medicinal Chemical Biology, Key 
      Laboratory of Bioactive Materials for Ministry of Education, Nankai University, 
      Tianjin, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180325
PL  - United States
TA  - J Cell Biochem
JT  - Journal of cellular biochemistry
JID - 8205768
RN  - 0 (AG-1031)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (MAP1LC3A protein, human)
RN  - 0 (MAP1LC3B protein, human)
RN  - 0 (Microtubule-Associated Proteins)
RN  - 0 (NOTCH1 protein, human)
RN  - 0 (Organic Chemicals)
RN  - 0 (Receptor, Notch1)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents/*pharmacology
MH  - Apoptosis/*drug effects
MH  - Autophagy/*drug effects
MH  - Brain Neoplasms/drug therapy/metabolism/*pathology
MH  - Cell Proliferation
MH  - Gene Expression Regulation, Neoplastic/*drug effects
MH  - Glioma/drug therapy/metabolism/*pathology
MH  - Microtubule-Associated Proteins/genetics/metabolism
MH  - Organic Chemicals/*pharmacology
MH  - Rats
MH  - Receptor, Notch1/genetics/*metabolism
MH  - Signal Transduction
MH  - TOR Serine-Threonine Kinases/genetics/metabolism
MH  - Tumor Cells, Cultured
OTO - NOTNLM
OT  - AG-1031
OT  - C6 cells
OT  - Notch-1
OT  - apoptosis
OT  - autophagy
EDAT- 2018/03/27 06:00
MHDA- 2019/05/09 06:00
CRDT- 2018/03/26 06:00
PHST- 2017/07/31 00:00 [received]
PHST- 2018/02/02 00:00 [accepted]
PHST- 2018/03/27 06:00 [pubmed]
PHST- 2019/05/09 06:00 [medline]
PHST- 2018/03/26 06:00 [entrez]
AID - 10.1002/jcb.26781 [doi]
PST - ppublish
SO  - J Cell Biochem. 2018 Jul;119(7):5893-5903. doi: 10.1002/jcb.26781. Epub 2018 Mar 
      25.