PMID- 28488118
OWN - NLM
STAT- MEDLINE
DCOM- 20171201
LR  - 20180710
IS  - 1559-0291 (Electronic)
IS  - 0273-2289 (Linking)
VI  - 183
IP  - 4
DP  - 2017 Dec
TI  - Isoliquiritigenin Induces Cytotoxicity in PC-12 Cells In Vitro.
PG  - 1173-1190
LID - 10.1007/s12010-017-2491-7 [doi]
AB  - Isoliquiritigenin (ISL) has been reported to have a wide range of biological 
      activities. This study evaluated the cytotoxic effect of ISL on norvegicus 
      pheochromocytoma cell line (PC-12 cells) and its possible molecular mechanism. 
      The cytotoxicity in vitro of ISL against PC-12 cells was investigated by MTT 
      assay. The migration and invasion of PC-12 cells were performed by scratch test 
      and transwell assay. Apoptosis was evaluated by microscopy and flow cytometry. 
      The reactive oxygen species (ROS) and mitochondrial membrane potential were 
      studied by fluorescent microscopy. DNA damage of PC-12 cells was analyzed by 
      comet assay. The protein expression of caspase, Bcl-2 family member, 
      autophagy-associated protein Beclin-1, and LC3 was detected by western blot. The 
      autophagy of PC-12 cells was investigated by acridine orange (AO) and 
      monodansylcadaverine (MDC) staining. The IC(50) value of ISL against PC-12 cell 
      is 17.8 +/- 1.8 muM. ISL could suppress PC-12 cell migration and invasion. 
      AO/ethidium bromide staining and flow cytometry suggested that ISL caused 
      apoptosis of PC-12 cells. Significant DNA damages of PC-12 cells treated with ISL 
      were observed in a comet assay. ISL inhibited the cell growth of PC-12 cells at S 
      phase. Exposure of PC-12 cells to ISL increased the levels of cellular reactive 
      oxygen species (ROS) and decreased the mitochondrial membrane potential. 
      Additionally, ISL trigged the release of cytochrome c from the mitochondria to 
      the cytoplasm. The expression levels of caspase-9, caspase-3, caspase-7, Bax, and 
      Bim were upregulated, whereas the expression levels of Bcl-2 and Bcl-x were 
      downregulated. AO and monodansylcadaverine (MDC) staining assay showed that ISL 
      caused autophagy of PC-12 cells. The upregulation of protein Beclin-1 and LC3 was 
      observed in PC-12 cells. Therefore, the results show that ISL induces apoptosis 
      of PC-12 cells through ROS-mediated activation of the intrinsic 
      mitochondria-cytochrome c-caspase protease mechanism and causes the autophagy of 
      PC-12 cells. Graphical Abstract The in vitro cytotoxicity, apoptosis, comet 
      assay, ROS, mitochondrial membrane potential, cell cycle arrest, autophagy, and 
      western blot induced by ISL were investigated.
FAU - Yang, Hui-Hui
AU  - Yang HH
AD  - School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, 510006, 
      People's Republic of China.
FAU - Zhang, Cheng
AU  - Zhang C
AD  - School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, 510006, 
      People's Republic of China.
FAU - Lai, Shang-Hai
AU  - Lai SH
AD  - School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, 510006, 
      People's Republic of China.
FAU - Zeng, Chuan-Chuan
AU  - Zeng CC
AD  - School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, 510006, 
      People's Republic of China.
FAU - Liu, Yun-Jun
AU  - Liu YJ
AD  - School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, 510006, 
      People's Republic of China. lyjche@163.com.
AD  - Guangdong Cosmetics Engineering and Technology Research Center, Guangzhou, 
      510006, People's Republic of China. lyjche@163.com.
FAU - Wang, Xiu-Zhen
AU  - Wang XZ
AD  - School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, 510006, 
      People's Republic of China. wxzqq1234@163.com.
LA  - eng
GR  - 2013LYM0047/Priority Academic Program Development of Guangdong Higher Education 
      Institutions/
GR  - 2016A030313728/Natural Science Foundation of Guangdong Province/
PT  - Journal Article
DEP - 20170509
PL  - United States
TA  - Appl Biochem Biotechnol
JT  - Applied biochemistry and biotechnology
JID - 8208561
RN  - 0 (Beclin-1)
RN  - 0 (Becn1 protein, rat)
RN  - 0 (Chalcones)
RN  - 0 (Cytotoxins)
RN  - 0 (LC3 protein, rat)
RN  - 0 (Microtubule-Associated Proteins)
RN  - 0 (Reactive Oxygen Species)
RN  - B9CTI9GB8F (isoliquiritigenin)
SB  - IM
MH  - Animals
MH  - Apoptosis/*drug effects
MH  - Beclin-1/metabolism
MH  - Chalcones/*pharmacology
MH  - Cytotoxins/*pharmacology
MH  - Membrane Potential, Mitochondrial/*drug effects
MH  - Microtubule-Associated Proteins/metabolism
MH  - PC12 Cells
MH  - Rats
MH  - Reactive Oxygen Species/*metabolism
OTO - NOTNLM
OT  - Apoptosis
OT  - Autophagy
OT  - Cell invasion
OT  - Isoliquiritigenin
OT  - Mitochondria
EDAT- 2017/05/11 06:00
MHDA- 2017/12/02 06:00
CRDT- 2017/05/11 06:00
PHST- 2017/03/05 00:00 [received]
PHST- 2017/04/24 00:00 [accepted]
PHST- 2017/05/11 06:00 [pubmed]
PHST- 2017/12/02 06:00 [medline]
PHST- 2017/05/11 06:00 [entrez]
AID - 10.1007/s12010-017-2491-7 [pii]
AID - 10.1007/s12010-017-2491-7 [doi]
PST - ppublish
SO  - Appl Biochem Biotechnol. 2017 Dec;183(4):1173-1190. doi: 
      10.1007/s12010-017-2491-7. Epub 2017 May 9.