PMID- 25213258
OWN - NLM
STAT- MEDLINE
DCOM- 20160201
LR  - 20211203
IS  - 1098-2744 (Electronic)
IS  - 0899-1987 (Linking)
VI  - 54
IP  - 11
DP  - 2015 Nov
TI  - Oroxylin A induces autophagy in human malignant glioma cells via the 
      mTOR-STAT3-Notch signaling pathway.
PG  - 1363-75
LID - 10.1002/mc.22212 [doi]
AB  - Autophagy is a tightly-regulated catabolic pathway involving degradation of 
      cellular proteins, cytoplasm and organelles. Recent evidence suggests that 
      autophagy plays a potential role in cell death as a tumor suppressor and that its 
      induction especially in combination with apoptosis could be beneficial. It 
      remains unclear if all cancer cells behave the same mechanism when autophagy is 
      induced. Although mammalian target of rapamycin (mTOR) is well known as a 
      negative regulator of autophagy, the relationship between signal transducer and 
      activator of transcription 3 (STAT3) and autophagy has not yet been investigated. 
      Oroxylin A, a natural mono-flavonoid extracted from Scutellariae radix, is a 
      promising therapeutic agent for treating multiple cancers. Here we investigated 
      the mechanism underlying the effect of oroxylin A on malignant glioma cells. We 
      showed that oroxylin A inhibited the proliferation of malignant glioma cells by 
      inducing autophagy in a dose- and time-dependent manner. Oroxylin A treatment 
      inhibits the AKT and ERK activation and the downstream phosphorylation level of 
      mTOR and STAT3. In addition, oroxylin A treatment decreases the expression of 
      Notch-1 and myeloid cell leukemia-1 (Mcl-1) but upregulates Beclin 1, the key 
      autophagy-related protein. 3-MA (autophagy inhibitor) or knockdown of Beclin 1 
      partially can rescue cells from oroxylin A-induced autophagic cell death. In 
      contrast, knockdown of STAT3 aggravates oroxylin A-induced autophagic cell death. 
      Our data reveal an important role of autophagy in enhancing cell death induced by 
      oroxylin A and conclude that oroxylin A exerts anti-malignant glioma proficiency 
      by inducing autophagy via the ERK/AKT-mTOR-STAT3-Notch signaling cascade.
CI  - (c) 2014 Wiley Periodicals, Inc.
FAU - Zou, Meijuan
AU  - Zou M
AD  - Department of Pharmacology, Nanjing Medical University, Nanjing, Jiangsu, China.
FAU - Hu, Chen
AU  - Hu C
AD  - Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical 
      University, Nanjing, Jiangsu, China.
FAU - You, Qidong
AU  - You Q
AD  - Jiangsu Center for Pharmacodynamics Research and Evaluation, China Pharmaceutical 
      University, Nanjing, Jiangsu, China.
FAU - Zhang, Aixia
AU  - Zhang A
AD  - School of Pharmacy, Nanjing Medical University, Nanjing, Jiangsu, China.
FAU - Wang, Xuerong
AU  - Wang X
AD  - Department of Pharmacology, Nanjing Medical University, Nanjing, Jiangsu, China.
FAU - Guo, Qinglong
AU  - Guo Q
AD  - Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical 
      University, Nanjing, Jiangsu, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140911
PL  - United States
TA  - Mol Carcinog
JT  - Molecular carcinogenesis
JID - 8811105
RN  - 0 (Apoptosis Regulatory Proteins)
RN  - 0 (BECN1 protein, human)
RN  - 0 (Beclin-1)
RN  - 0 (Flavonoids)
RN  - 0 (MCL1 protein, human)
RN  - 0 (Membrane Proteins)
RN  - 0 (Myeloid Cell Leukemia Sequence 1 Protein)
RN  - 0 (NOTCH1 protein, human)
RN  - 0 (Receptor, Notch1)
RN  - 0 (STAT3 Transcription Factor)
RN  - 0 (STAT3 protein, human)
RN  - 53K24Z586G (5,7-dihydroxy-6-methoxy-2-phenylchromen-4-one)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Apoptosis Regulatory Proteins/genetics
MH  - Autophagy/*drug effects/genetics
MH  - Beclin-1
MH  - Cell Line, Tumor
MH  - Cell Proliferation/drug effects/genetics
MH  - Flavonoids/*pharmacology
MH  - Glioma/*drug therapy/genetics
MH  - Humans
MH  - MAP Kinase Signaling System/drug effects/genetics
MH  - Membrane Proteins/genetics
MH  - Myeloid Cell Leukemia Sequence 1 Protein/*genetics
MH  - Phosphorylation/drug effects/genetics
MH  - Proto-Oncogene Proteins c-akt/genetics
MH  - Receptor, Notch1/*genetics
MH  - STAT3 Transcription Factor/*genetics
MH  - Signal Transduction/drug effects/genetics
MH  - TOR Serine-Threonine Kinases/*genetics
MH  - Up-Regulation/drug effects/genetics
OTO - NOTNLM
OT  - autophagy
OT  - cell death
OT  - mTOR-STAT3-Notch
OT  - malignant glioma cells
OT  - oroxylin A
EDAT- 2014/09/13 06:00
MHDA- 2016/02/02 06:00
CRDT- 2014/09/13 06:00
PHST- 2014/01/24 00:00 [received]
PHST- 2014/06/29 00:00 [revised]
PHST- 2014/07/09 00:00 [accepted]
PHST- 2014/09/13 06:00 [entrez]
PHST- 2014/09/13 06:00 [pubmed]
PHST- 2016/02/02 06:00 [medline]
AID - 10.1002/mc.22212 [doi]
PST - ppublish
SO  - Mol Carcinog. 2015 Nov;54(11):1363-75. doi: 10.1002/mc.22212. Epub 2014 Sep 11.