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p , p ′‐Dichlorodiphenyltrichloroethane promotes aerobic glycolysis via reactive oxygen species–mediated extracellular signal‐regulated kinase/M2 isoform of pyruvate kinase (PKM2) signaling in colorectal cancer cells
Author(s) -
Song Li,
Dong Ningning,
Li Zhuoyu
Publication year - 2020
Publication title -
environmental toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.813
H-Index - 77
eISSN - 1522-7278
pISSN - 1520-4081
DOI - 10.1002/tox.22869
Subject(s) - pkm2 , pyruvate kinase , anaerobic glycolysis , glycolysis , reactive oxygen species , kinase , chemistry , signal transduction , downregulation and upregulation , extracellular , biochemistry , biology , medicine , metabolism , gene
Aerobic glycolysis is crucial to tumor cells to acquire energy for proliferation and metastasis. Dichlorodiphenyltrichloroethane (DDT), which is a persistent organic pollutant, has been associated with colorectal cancer (CRC) progressions, but the influence of p , p ′‐DDT on CRC cell metabolism remains unclear. This study showed that exposure to low concentrations of p , p ′‐DDT from 10 −11 to 10 −7 M for 48 hours significantly increased glucose uptake and lactate production in colorectal adenocarcinoma cells, which were accompanied by the upregulation of proteins associated with aerobic glycolysis including glucose transporter1, lactate dehydrogenase A, and PDH kinase. We found p , p ′‐DDT elevated the expression and nucleus translocation of M2 isoform of pyruvate kinase (PKM2), which was responsible for p , p ′‐DDT–induced enhancement of aerobic glycolysis. Moreover, extracellular signal‐regulated kinase (ERK1/2) activation by p , p ′‐DDT modulated the impacts of p , p ′‐DDT on PKM2 and aerobic glycolysis. Treatment of p , p ′‐DDT increased intracellular reactive oxygen species (ROS). N ‐acetyl‐ L ‐cysteine, an ROS inhibitor, prevented p , p ′‐DDT–induced promotion of aerobic glycolysis, ERK1/2 activation, upregulation, and nucleus translocation of PKM2. Taken together, these results demonstrated that p , p ′‐DDT promotes aerobic glycolysis via ROS‐mediated ERK/PKM2 signaling.