PMID- 23128449
OWN - NLM
STAT- MEDLINE
DCOM- 20140109
LR  - 20181202
IS  - 1791-2431 (Electronic)
IS  - 1021-335X (Linking)
VI  - 29
IP  - 1
DP  - 2013 Jan
TI  - Knockdown of Nrf2 enhances autophagy induced by temozolomide in U251 human glioma 
      cell line.
PG  - 394-400
LID - 10.3892/or.2012.2115 [doi]
AB  - Glioblastoma multiforme (GBM) and oxidative stress are closely linked. Oxidative 
      stress affects many signaling pathways and may cause the induction of autophagy. 
      The NF-E2-related factor 2 (Nrf2)/Kelch-like ECH-associated protein 1 (Keap1) 
      signaling pathway is the main pathway responsible for cell defense against 
      oxidative stress and Nrf2 is a critical transcription factor related with cancer 
      multidrug resistance. However, the relation between Nrf2 and regulation of 
      autophagy is not well understood. In this study, we used temozolomide (TMZ), 
      which inhibited the viability of GBM cells mainly by inducing autophagic cell 
      death and explored the role of Nrf2 downregulation on autophagy induced by TMZ in 
      GBM cells. In U251-Si-Nrf2 48 h after transfection the protein levels of Nrf2 
      were significantly downregulated, while the protein levels of LC3B-II increased 
      by western blot analysis. Knockdown of Nrf2 also led to a significant increase of 
      autophagic vacuoles and acidic vesicular organelles (AVOs), revealed by 
      trans-mission electron microscopy (TEM) and acridine orange (AO) staining using 
      flow cytometry. Collectively, these findings demonstrate that knockdown of Nrf2 
      can enhance the basal level of autophagy in the U251 glioma cell line. 
      Furthermore, after the treatment with TMZ (100 microM) for 3 days, the U251-Si-Nrf2 
      transfected cells showed less viability rate by cell counting kit-8 (CCK-8) assay 
      and the levels of autophagy increased obviously through analysis of western blot 
      and AO staining using flow cytometry. Taken together, our results suggest that 
      knockdown of Nrf2 may enhance autophagy induced by TMZ in the U251 glioma cell 
      line, which should be further evaluated for novel anticancer activity.
FAU - Zhou, Yuan
AU  - Zhou Y
AD  - Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing 
      University, Nanjing 210002, PR China.
FAU - Wang, Han-Dong
AU  - Wang HD
FAU - Zhu, Lin
AU  - Zhu L
FAU - Cong, Zi-Xiang
AU  - Cong ZX
FAU - Li, Ning
AU  - Li N
FAU - Ji, Xiang-Jun
AU  - Ji XJ
FAU - Pan, Hao
AU  - Pan H
FAU - Wang, Jia-Wei
AU  - Wang JW
FAU - Li, Wan-Chun
AU  - Li WC
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20121031
PL  - Greece
TA  - Oncol Rep
JT  - Oncology reports
JID - 9422756
RN  - 0 (Antineoplastic Agents, Alkylating)
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (NFE2L2 protein, human)
RN  - 0 (RNA, Small Interfering)
RN  - 7GR28W0FJI (Dacarbazine)
RN  - YF1K15M17Y (Temozolomide)
SB  - IM
MH  - Antineoplastic Agents, Alkylating/*pharmacology
MH  - Apoptosis/*drug effects
MH  - Autophagy/*drug effects
MH  - Blotting, Western
MH  - Brain Neoplasms/drug therapy/metabolism/*pathology
MH  - Dacarbazine/*analogs & derivatives/pharmacology
MH  - Down-Regulation
MH  - Flow Cytometry
MH  - Fluorescent Antibody Technique
MH  - Glioma/drug therapy/metabolism/*pathology
MH  - Humans
MH  - Microscopy, Electron, Transmission
MH  - NF-E2-Related Factor 2/*antagonists & inhibitors/genetics/metabolism
MH  - RNA, Small Interfering/genetics
MH  - Temozolomide
MH  - Tumor Cells, Cultured
EDAT- 2012/11/07 06:00
MHDA- 2014/01/10 06:00
CRDT- 2012/11/07 06:00
PHST- 2012/09/04 00:00 [received]
PHST- 2012/10/18 00:00 [accepted]
PHST- 2012/11/07 06:00 [entrez]
PHST- 2012/11/07 06:00 [pubmed]
PHST- 2014/01/10 06:00 [medline]
AID - 10.3892/or.2012.2115 [doi]
PST - ppublish
SO  - Oncol Rep. 2013 Jan;29(1):394-400. doi: 10.3892/or.2012.2115. Epub 2012 Oct 31.