title: Tris(2-chloroethyl)phosphate-induced cell growth arrest via attenuation of SIRT1-independent PI3K/Akt/mTOR pathway.
abstract: Tris(2-chloroethyl)phosphate (TCEP) as an organophosphorus flame retardant and plasticizer has been widely used in industrial and household products. It not only was detected in residential indoor air and dust, surface and drinking water, but also in human plasma and breast milk, and tissue samples of liver, kidneys and brain from rodents. TCEP is classified as carcinogenic category 2 and toxic for reproduction category 1B. Sufficient evidence from experimental animals indicated carcinogenicity of TCEP in the liver, and kidneys as well as cell loss in the brain. However, the underlying mechanisms of TCEP-induced hepatotoxicity are mostly unknown. We investigated the in vitro effects of TCEP as well as TCEP-induced cell growth in the L02 and HepG2 cells through the PI3K/Akt/mTOR pathway. We found that TCEP reduced cell viability of these cell lines, induced the cell growth arrest, upregulated mRNA and protein levels of SIRT1, and attenuated the PI3K/Akt/mTOR pathway. However, growth arrest of the L02 and HepG2 cells were aggravated after inhibiting the SIRT1 expression with EX-527. The findings above suggested that TCEP induced the cell growth arrest of L02 and HepG2 cells via attenuation of the SIRT1-independent PI3K/Akt/mTOR pathway. Copyright © 2015 John Wiley & Sons, Ltd.
authors.affiliation: Department of Occupational and Environmental Health, Wuhan, Hubei, People's Republic of China.|Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China.
authors.forename: Wenjuan
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Occupational and Environmental Health, Wuhan, Hubei, People's Republic of China.|Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China.
authors.forename: Youjian
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Occupational and Environmental Health, Wuhan, Hubei, People's Republic of China.|Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China.
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Occupational and Environmental Health, Wuhan, Hubei, People's Republic of China.|Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China.
authors.forename: Tian
authors.initials: T
authors.lastname: Xu
authors.affiliation: Department of Occupational and Environmental Health, Wuhan, Hubei, People's Republic of China.|Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Huang
authors.affiliation: Department of Occupational and Environmental Health, Wuhan, Hubei, People's Republic of China.|Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China.
authors.forename: Wenjun
authors.initials: W
authors.lastname: Yin
authors.affiliation: Department of Occupational and Environmental Health, Wuhan, Hubei, People's Republic of China.|Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Occupational and Environmental Health, Wuhan, Hubei, People's Republic of China.|Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xiong
authors.affiliation: Department of Occupational and Environmental Health, Wuhan, Hubei, People's Republic of China.|Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China.
authors.forename: Wenhong
authors.initials: W
authors.lastname: Lu
authors.affiliation: Department of Occupational and Environmental Health, Wuhan, Hubei, People's Republic of China.|Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Zheng
authors.affiliation: Department of Occupational and Environmental Health, Wuhan, Hubei, People's Republic of China.|Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Yuan
mesh_terms: D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005411:Flame Retardants / Q000633:toxicity; D056945:Hep G2 Cells; D006801:Humans; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010755:Organophosphates / Q000633:toxicity*; D010084:Oxidation-Reduction; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D010968:Plasticizers / Q000633:toxicity; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism*; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D005411:Flame Retardants; D010755:Organophosphates; D019869:Phosphatidylinositol 3-Kinases; D010968:Plasticizers; D051057:Proto-Oncogene Proteins c-akt; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D056564:Sirtuin 1; D058570:TOR Serine-Threonine Kinases; C031324:tris(chloroethyl)phosphate; C546842:MTOR protein, human; C447939:SIRT1 protein, human
keywords: Akt; ROS; SIRT1; growth arrest; mTOR; tris(2-chloroethyl)phosphate