Tris(2-chloroethyl)phosphate-induced cell growth arrest via attenuation of SIRT1-independent PI3K/Akt/mTOR pathway

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• 作者：Wenjuan Zhang ; Youjian Zhang ; Zhiyuan Wang ; Tian Xu ; Cheng Huang ; Wenjun Yin ; Jing Wang ; Wei Xiong ; Wenhong Lu ; Hongyan Zheng and Jing Yuan
• 刊名：Journal of Applied Toxicology
• 出版年：2016
• 出版时间：July 2016
• 年：2016
• 卷：36
• 期：7
• 页码：914-924
• 全文大小：4193K
• ISSN：1099-1263

文摘

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