PMID- 31686145
OWN - NLM
STAT- MEDLINE
DCOM- 20200326
LR  - 20200326
IS  - 1432-0614 (Electronic)
IS  - 0175-7598 (Linking)
VI  - 103
IP  - 23-24
DP  - 2019 Dec
TI  - Autophagy suppression enhances DNA damage and cell death upon treatment with PARP 
      inhibitor Niraparib in laryngeal squamous cell carcinoma.
PG  - 9557-9568
LID - 10.1007/s00253-019-10148-y [doi]
AB  - Although poly (ADP-ribose) polymerase (PARP) inhibitors, as anti-tumor drugs 
      targeting the DNA damage response (DDR), have been used for the therapy of 
      various tumors, few researches reported their effect on laryngeal squamous cell 
      carcinoma (LSCC). Here, we first discovered that the PARP-1/2 inhibitor Niraparib 
      could simultaneously induce cell growth inhibition and autophagy in LSCC TU212 
      and TU686 cells. Niraparib decelerated cell cycle of LSCC by arresting G1 phase 
      and preventing the cells from entering S phase. DNA lesions were also observed 
      upon Niraparib treatment as evidenced by the accumulation of gammaH2AX and abatement 
      of pRB expression. In addition, autophagy generation was confirmed by the 
      observation of autophagosomes, LC3-positive autophagy-like vacuoles, and obvious 
      conversion of LC3-I to LC3-II. Moreover, blocking autophagy enhanced 
      Niraparib-induced growth inhibition and DNA lesions. Further studies suggested 
      that autophagy suppression could obstruct the activation of checkpoint kinase 1 
      (Chk1) through elevating proteasomal activity and then impair the capacity of 
      homologous recombination (HR), thereby improving the anti-LSCC efficiency of 
      Niraparib. Collectively, these findings suggested that simultaneous targeting of 
      Niraparib and autophagy might be a promising therapeutic schedule for LSCC in 
      clinic.
FAU - Ji, Yunxiang
AU  - Ji Y
AD  - Department of Otorhinolaryngology-Head and Neck Surgery, Huashan Hospital, Fudan 
      University, Shanghai, China.
FAU - Wang, Qian
AU  - Wang Q
AD  - Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, 
      200032, China.
FAU - Zhao, Qian
AU  - Zhao Q
AD  - Department of Biological Medicines, School of Pharmacy, Fudan University, 
      Shanghai, 201203, China.
FAU - Zhao, Shuwei
AU  - Zhao S
AD  - Department of Otolaryngology, Changzheng Hospital, The Second Military Medical 
      University, Shanghai, 200003, China.
FAU - Li, Li
AU  - Li L
AD  - Department of Otolaryngology, Changzheng Hospital, The Second Military Medical 
      University, Shanghai, 200003, China. lili1982007@smmu.edu.cn.
FAU - Sun, Guangbin
AU  - Sun G
AD  - Department of Otorhinolaryngology-Head and Neck Surgery, Huashan Hospital, Fudan 
      University, Shanghai, China. sgb223@hotmail.com.
FAU - Ye, Li
AU  - Ye L
AUID- ORCID: 0000-0001-5303-2549
AD  - Department of Biological Medicines, School of Pharmacy, Fudan University, 
      Shanghai, 201203, China. yelil@fudan.edu.cn.
LA  - eng
GR  - 201444/Shanghai Municipal Population and Family Planning Commission/
GR  - 17ZR1438900/Natural Science Foundation of Shanghai/
GR  - 18431902800/Scientific and Innovative Action Plan of Shanghai/
PT  - Journal Article
DEP - 20191104
PL  - Germany
TA  - Appl Microbiol Biotechnol
JT  - Applied microbiology and biotechnology
JID - 8406612
RN  - 0 (Indazoles)
RN  - 0 (Piperidines)
RN  - 0 (Poly(ADP-ribose) Polymerase Inhibitors)
RN  - HMC2H89N35 (niraparib)
SB  - IM
MH  - Autophagic Cell Death/*drug effects
MH  - Cell Cycle/drug effects
MH  - Cell Line, Tumor
MH  - DNA Damage/*drug effects
MH  - Humans
MH  - Indazoles/*pharmacology
MH  - Laryngeal Neoplasms/drug therapy/*pathology
MH  - Piperidines/*pharmacology
MH  - Poly(ADP-ribose) Polymerase Inhibitors/*pharmacology
OTO - NOTNLM
OT  - Autophagy
OT  - DNA damage
OT  - Homologous recombination
OT  - Laryngeal squamous cell carcinoma
OT  - Poly (ADP-ribose) polymerase
EDAT- 2019/11/07 06:00
MHDA- 2020/03/27 06:00
CRDT- 2019/11/06 06:00
PHST- 2019/08/08 00:00 [received]
PHST- 2019/09/17 00:00 [accepted]
PHST- 2019/09/10 00:00 [revised]
PHST- 2019/11/07 06:00 [pubmed]
PHST- 2020/03/27 06:00 [medline]
PHST- 2019/11/06 06:00 [entrez]
AID - 10.1007/s00253-019-10148-y [pii]
AID - 10.1007/s00253-019-10148-y [doi]
PST - ppublish
SO  - Appl Microbiol Biotechnol. 2019 Dec;103(23-24):9557-9568. doi: 
      10.1007/s00253-019-10148-y. Epub 2019 Nov 4.