PMID- 31251971
OWN - NLM
STAT- MEDLINE
DCOM- 20190729
LR  - 20231213
IS  - 1879-3169 (Electronic)
IS  - 0378-4274 (Linking)
VI  - 313
DP  - 2019 Oct 1
TI  - 2,3'4,4',5-Pentachlorobiphenyl induces hepatocellular carcinoma cell 
      proliferation through pyruvate kinase M2-dependent glycolysis.
PG  - 108-119
LID - S0378-4274(18)31705-3 [pii]
LID - 10.1016/j.toxlet.2019.06.006 [doi]
AB  - Polychlorinated biphenyls (PCBs) are classic persistent organic pollutants (POPs) 
      and are associated with the progression of many cancers, including liver cancer. 
      The present study investigated the effect of 2,3'4,4',5-pentachlorobiphenyl 
      (PCB118) on hepatocellular carcinoma cell proliferation and its underlying 
      mechanisms. The results indicated that PCB118 exposure promotes the proliferation 
      and glycolysis of hepatocellular carcinoma SMMC-7721 cells. Moreover, PCB118 
      exposure increased the expression level of pyruvate kinase M2 (PKM2) and its 
      nuclear translocation, whereas treatment with PKM2 shRNA suppressed the induction 
      of cell proliferation and glycolysis by PCB118. PCB118 stimulated reactive oxygen 
      species (ROS) production by activating nicotinamide adenine dinucleotide 
      phosphate (NADPH) oxidase. Treatment with the antioxidants N-acetyl-L-cysteine 
      (NAC) and superoxide dismutase (SOD) prevented PCB118-induced effects on PKM2, 
      cell proliferation and glycolysis. Furthermore, we found that PCB118 activated 
      NADPH oxidase through the aryl hydrocarbon receptor (AhR) in SMMC-7721 cells. 
      Consistently, treatment with AhR shRNA suppressed PCB118-induced effects on PKM2, 
      cell proliferation and glycolysis. Overall, these results indicated that PCB118 
      promotes HCC cell proliferation via PKM2-dependent upregulation of glycolysis, 
      which is mediated by AhR/NADPH oxidase-induced ROS production.
CI  - Copyright (c) 2019 Elsevier B.V. All rights reserved.
FAU - Liang, Wenli
AU  - Liang W
AD  - Institute of Biotechnology, Key Laboratory of Chemical Biology and Molecular 
      Engineering of National Ministry of Education, Shanxi University, Taiyuan 030006, 
      China.
FAU - Zhang, Yuting
AU  - Zhang Y
AD  - Institute of Biotechnology, Key Laboratory of Chemical Biology and Molecular 
      Engineering of National Ministry of Education, Shanxi University, Taiyuan 030006, 
      China.
FAU - Song, Li
AU  - Song L
AD  - Institute of Biotechnology, Key Laboratory of Chemical Biology and Molecular 
      Engineering of National Ministry of Education, Shanxi University, Taiyuan 030006, 
      China. Electronic address: lsong@sxu.edu.cn.
FAU - Li, Zhuoyu
AU  - Li Z
AD  - Institute of Biotechnology, Key Laboratory of Chemical Biology and Molecular 
      Engineering of National Ministry of Education, Shanxi University, Taiyuan 030006, 
      China.
LA  - eng
PT  - Journal Article
DEP - 20190625
PL  - Netherlands
TA  - Toxicol Lett
JT  - Toxicology letters
JID - 7709027
RN  - 0 (AHR protein, human)
RN  - 0 (Basic Helix-Loop-Helix Transcription Factors)
RN  - 0 (Carcinogens, Environmental)
RN  - 0 (Carrier Proteins)
RN  - 0 (Membrane Proteins)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Receptors, Aryl Hydrocarbon)
RN  - 0 (Thyroid Hormones)
RN  - 2B2AQE8U50 (2,3',4,4',5-pentachlorobiphenyl)
RN  - DFC2HB4I0K (Polychlorinated Biphenyls)
RN  - EC 1.6.3.- (NADPH Oxidases)
MH  - Active Transport, Cell Nucleus
MH  - Basic Helix-Loop-Helix Transcription Factors/agonists/genetics/metabolism
MH  - Carcinogens, Environmental/*toxicity
MH  - Carcinoma, Hepatocellular/*enzymology/genetics/pathology
MH  - Carrier Proteins/genetics/*metabolism
MH  - Cell Line, Tumor
MH  - Cell Proliferation/*drug effects
MH  - Glycolysis/*drug effects
MH  - Humans
MH  - Liver Neoplasms/*enzymology/pathology
MH  - Membrane Proteins/genetics/*metabolism
MH  - NADPH Oxidases/metabolism
MH  - Polychlorinated Biphenyls/*toxicity
MH  - Reactive Oxygen Species/metabolism
MH  - Receptors, Aryl Hydrocarbon/agonists/genetics/metabolism
MH  - Signal Transduction/drug effects
MH  - Thyroid Hormones/genetics/*metabolism
MH  - Thyroid Hormone-Binding Proteins
OTO - NOTNLM
OT  - 2,3'4,4',5-Pentachlorobiphenyl
OT  - Cell proliferation
OT  - Glycolysis
OT  - Hepatocellular carcinoma cells
OT  - PKM2
EDAT- 2019/06/30 06:00
MHDA- 2019/07/30 06:00
CRDT- 2019/06/29 06:00
PHST- 2018/08/07 00:00 [received]
PHST- 2019/05/24 00:00 [revised]
PHST- 2019/06/21 00:00 [accepted]
PHST- 2019/06/30 06:00 [pubmed]
PHST- 2019/07/30 06:00 [medline]
PHST- 2019/06/29 06:00 [entrez]
AID - S0378-4274(18)31705-3 [pii]
AID - 10.1016/j.toxlet.2019.06.006 [doi]
PST - ppublish
SO  - Toxicol Lett. 2019 Oct 1;313:108-119. doi: 10.1016/j.toxlet.2019.06.006. Epub 
      2019 Jun 25.