PMID- 30821169
OWN - NLM
STAT- MEDLINE
DCOM- 20191218
LR  - 20191218
IS  - 1537-6524 (Electronic)
IS  - 1537-6516 (Linking)
VI  - 29
IP  - 6
DP  - 2019 Jul
TI  - Polychlorinated biphenyls promote cell survival through pyruvate kinase 
      M2-dependent glycolysis in HeLa cells.
PG  - 428-437
LID - 10.1080/15376516.2019.1584658 [doi]
AB  - It is well known that polychlorinated biphenyls (PCBs) are typical persistent 
      organic pollutants (POPs) in the environment. The present study investigated the 
      effects of three PCBs including 3,3',4,4',5-pentachlorobiphenyl (PCB126), 
      2,3',4,4',5-pentachlorobiphenyl (PCB118), and 2,2',4,4',5,5'-hexachlorobiphenyl 
      (PCB153) on human cervical carcinoma HeLa cell survival and the possible 
      underlying mechanisms. The results showed that PCB126, PCB118, or PCB153 exposure 
      for 48 h significantly promoted HeLa cell survival. Meanwhile, glucose 
      consumption, lactate production, and glycolysis-related proteins including 
      glucose transporter-1 (GLUT1), lactate dehydrogenase (LDHA), and pyruvate 
      dehydrogenase kinase (PDK) were remarkably elevated after three PCBs treatment, 
      indicated PCBs stimulating glycolysis. Moreover, we found that the expression and 
      nuclear distribution of PKM2 protein was significantly increased in PCB126, 
      PCB118, or PCB153-treated HeLa cells. However, the enzymatic activity of PKM2 was 
      reduced. In addition, the three congeners exposure elevated ROS levels and the 
      expression of NADPH oxidase subunits such as NOX2, p47(phox), and p40(phox). The 
      addition of antioxidant NAC antagonized the three PCBs-induced effects on PKM2, 
      cell survival, and glycolysis. Taken together, these results indicated that 
      PCB126, PCB118, or PCB153 exposure promotes cervical cancer HeLa cell survival by 
      PKM2-dependent upregulation of glycolysis, which is mediated by NADPH 
      oxidase-induced ROS production.
FAU - Zhang, Yuting
AU  - Zhang Y
AD  - a Institute of Biotechnology , Key Laboratory of Chemical Biology and Molecular 
      Engineering of National Ministry of Education, Shanxi University , Taiyuan , 
      China.
FAU - Song, Li
AU  - Song L
AD  - a Institute of Biotechnology , Key Laboratory of Chemical Biology and Molecular 
      Engineering of National Ministry of Education, Shanxi University , Taiyuan , 
      China.
FAU - Li, Zhuoyu
AU  - Li Z
AD  - a Institute of Biotechnology , Key Laboratory of Chemical Biology and Molecular 
      Engineering of National Ministry of Education, Shanxi University , Taiyuan , 
      China.
AD  - b College of Life Science , Zhejiang Chinese Medical University , Hangzhou , 
      China.
LA  - eng
PT  - Journal Article
DEP - 20190416
PL  - England
TA  - Toxicol Mech Methods
JT  - Toxicology mechanisms and methods
JID - 101134521
RN  - 0 (Environmental Pollutants)
RN  - 0 (Reactive Oxygen Species)
RN  - 2B2AQE8U50 (2,3',4,4',5-pentachlorobiphenyl)
RN  - DFC2HB4I0K (Polychlorinated Biphenyls)
RN  - EC 1.6.3.- (NADPH Oxidases)
RN  - EC 2.7.1.40 (Pyruvate Kinase)
RN  - TSH69IA9XF (3,4,5,3',4'-pentachlorobiphenyl)
RN  - ZRU0C9E32O (2,4,5,2',4',5'-hexachlorobiphenyl)
SB  - IM
MH  - Cell Survival/drug effects
MH  - Environmental Pollutants/*toxicity
MH  - Glycolysis/*drug effects
MH  - HeLa Cells
MH  - Humans
MH  - NADPH Oxidases/genetics
MH  - Polychlorinated Biphenyls/*toxicity
MH  - Pyruvate Kinase/*metabolism
MH  - Reactive Oxygen Species/metabolism
MH  - Up-Regulation
OTO - NOTNLM
OT  - PKM2
OT  - Polychlorinated biphenyls
OT  - ROS
OT  - glycolysis
OT  - human cervical carcinoma
EDAT- 2019/03/02 06:00
MHDA- 2019/12/19 06:00
CRDT- 2019/03/02 06:00
PHST- 2019/03/02 06:00 [pubmed]
PHST- 2019/12/19 06:00 [medline]
PHST- 2019/03/02 06:00 [entrez]
AID - 10.1080/15376516.2019.1584658 [doi]
PST - ppublish
SO  - Toxicol Mech Methods. 2019 Jul;29(6):428-437. doi: 10.1080/15376516.2019.1584658. 
      Epub 2019 Apr 16.