PMID- 28352997
OWN - NLM
STAT- MEDLINE
DCOM- 20171221
LR  - 20211204
IS  - 1432-0614 (Electronic)
IS  - 0175-7598 (Linking)
VI  - 101
IP  - 12
DP  - 2017 Jun
TI  - Deprivation of asparagine triggers cytoprotective autophagy in laryngeal squamous 
      cell carcinoma.
PG  - 4951-4961
LID - 10.1007/s00253-017-8221-9 [doi]
AB  - Laryngeal squamous cell carcinoma (LSCC), one of the most common malignancies in 
      the head and neck, has poor prognosis and high mortality. The need of novel and 
      effective treatment for LSCC is urgent. Asparaginase, an enzyme-depriving 
      asparagine, has been employed for the treatment of various cancers. In this 
      study, we reported for the first time that asparaginase could induce remarkable 
      cytotoxicity and caspase-dependent apoptosis in human LSCC Tu212 and Tu686 cells. 
      Meanwhile, autophagy was triggered by asparaginase in LSCC cells, which was 
      confirmed by accumulation of autophagosomes and the conversion of light chain 3-I 
      (LC3-I) to LC3-II. Importantly, inhibition of autophagy by chloroquine (CQ) 
      significantly enhanced asparaginase-induced cytotoxicity, indicating that 
      autophagy has a cytoprotective role in asparaginase-treated LSCC cells. 
      Meanwhile, we found that mitochondrial-originated reactive oxygen species (ROS) 
      participated in asparaginase-induced autophagy and cytotoxicity. 
      N-acetyl-L-cysteine (NAC), a common antioxidant, was employed to scavenge ROS, 
      and our results demonstrated that NAC could significantly block 
      asparaginase-induced autophagy and attenuate asparaginase-induced cytotoxicity, 
      indicating that intracellular ROS played a crucial role in asparagine deprivation 
      therapy. Furthermore, western blot analysis showed that asparaginase-induced 
      autophagy was mediated by inactivation of Akt/mTOR and activation of the Erk 
      signaling pathway in Tu212 and Tu686 cells. Therefore, these results indicated 
      the protective role of autophagy in asparaginase-treated LSCC cells and provided 
      a new attractive therapeutic strategy for LSCC by asparaginase alone or in 
      combination with autophagic inhibitors.
FAU - Ji, Yunxiang
AU  - Ji Y
AD  - Department of Otolaryngology, Changzheng Hospital, The Second Military Medical 
      University, No. 415 Fengyang Road, Shanghai, 200003, People's Republic of China.
FAU - Li, Li
AU  - Li L
AD  - Department of Otolaryngology, Changzheng Hospital, The Second Military Medical 
      University, No. 415 Fengyang Road, Shanghai, 200003, People's Republic of China.
FAU - Tao, Qilei
AU  - Tao Q
AD  - Department of Otolaryngology, Changzheng Hospital, The Second Military Medical 
      University, No. 415 Fengyang Road, Shanghai, 200003, People's Republic of China.
FAU - Zhang, Xuyao
AU  - Zhang X
AD  - Department of Microbiological and Biochemical Pharmacy & The Key Laboratory of 
      Smart Drug Delivery, Ministry of Education, School of Pharmacy, Fudan University, 
      No. 826 Zhangheng Road, Shanghai, 201203, People's Republic of China.
FAU - Luan, Jingyun
AU  - Luan J
AD  - Department of Microbiological and Biochemical Pharmacy & The Key Laboratory of 
      Smart Drug Delivery, Ministry of Education, School of Pharmacy, Fudan University, 
      No. 826 Zhangheng Road, Shanghai, 201203, People's Republic of China.
FAU - Zhao, Shuwei
AU  - Zhao S
AD  - Department of Otolaryngology, Changzheng Hospital, The Second Military Medical 
      University, No. 415 Fengyang Road, Shanghai, 200003, People's Republic of China. 
      shuweizhao@yahoo.com.
FAU - Liu, Huanhai
AU  - Liu H
AD  - Department of Otolaryngology, Changzheng Hospital, The Second Military Medical 
      University, No. 415 Fengyang Road, Shanghai, 200003, People's Republic of China. 
      Liuhuanhaiok@126.com.
FAU - Ju, Dianwen
AU  - Ju D
AD  - Department of Microbiological and Biochemical Pharmacy & The Key Laboratory of 
      Smart Drug Delivery, Ministry of Education, School of Pharmacy, Fudan University, 
      No. 826 Zhangheng Road, Shanghai, 201203, People's Republic of China. 
      dianwenju@fudan.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20170328
PL  - Germany
TA  - Appl Microbiol Biotechnol
JT  - Applied microbiology and biotechnology
JID - 8406612
RN  - 0 (Reactive Oxygen Species)
RN  - 7006-34-0 (Asparagine)
RN  - 886U3H6UFF (Chloroquine)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 3.5.1.1 (Asparaginase)
RN  - WYQ7N0BPYC (Acetylcysteine)
SB  - IM
MH  - Acetylcysteine/pharmacology
MH  - Apoptosis/drug effects
MH  - Asparaginase/metabolism/*pharmacology
MH  - Asparagine/*metabolism
MH  - Autophagy/*drug effects
MH  - Carcinoma, Squamous Cell/drug therapy/*physiopathology
MH  - Cell Line, Tumor
MH  - Chloroquine/pharmacology
MH  - Humans
MH  - Laryngeal Neoplasms/*physiopathology/*therapy
MH  - Mitochondria/drug effects/metabolism
MH  - Reactive Oxygen Species/metabolism
MH  - Signal Transduction/drug effects
MH  - TOR Serine-Threonine Kinases/metabolism
OTO - NOTNLM
OT  - Apoptosis
OT  - Asparaginase
OT  - Autophagy
OT  - Laryngeal squamous cell carcinoma
OT  - Reactive oxygen species
EDAT- 2017/03/30 06:00
MHDA- 2017/12/22 06:00
CRDT- 2017/03/30 06:00
PHST- 2017/01/16 00:00 [received]
PHST- 2017/03/04 00:00 [accepted]
PHST- 2017/02/27 00:00 [revised]
PHST- 2017/03/30 06:00 [pubmed]
PHST- 2017/12/22 06:00 [medline]
PHST- 2017/03/30 06:00 [entrez]
AID - 10.1007/s00253-017-8221-9 [pii]
AID - 10.1007/s00253-017-8221-9 [doi]
PST - ppublish
SO  - Appl Microbiol Biotechnol. 2017 Jun;101(12):4951-4961. doi: 
      10.1007/s00253-017-8221-9. Epub 2017 Mar 28.