Int. J. Mol. Sci. 2014, 15(3), 4019-4030; doi:10.3390/ijms15034019
Article

The Effect and Mechanism of Tamoxifen-Induced Hepatocyte Steatosis in Vitro

Received: 14 January 2014; in revised form: 11 February 2014 / Accepted: 19 February 2014 / Published: 5 March 2014
(This article belongs to the collection Molecular Mechanisms of Human Liver Diseases)
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract: The aim of this study was to determine the effect and mechanism of tamoxifen (TAM)-induced steatosis in vitro. HepG 2 (Human hepatocellular liver carcinoma cell line) cells were treated with different concentrations of TAM for 72 h. Steatosis of hepatocytes was determined after Oil Red O staining and measurement of triglyceride (TG) concentration. The expressions of genes in the TG homeostasis pathway, including sterol regulatory element-binding protein-1c (SREBP-1c), peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer-binding protein α (C/EBPα), fatty acid synthase (FAS), acetyl-CoA carboxylase (ACC), stearoyl-CoA desaturase (SCD), carnitine palmitoyltransferase 1 (CPT1) and microsomal triglyceride transfer protein (MTP), were examined using quantitative real-time PCR and Western blot analysis. Cell proliferation was examined using the cell counting kit-8 (CCK-8) assay. We found that hepatocytes treated with TAM had: (1) induced hepatocyte steatosis and increased hepatocyte TG; (2) upregulation of SREBP-1c, FAS, ACC, SCD and MTP mRNA expressions (300%, 600%, 70%, 130% and 160%, respectively); (3) corresponding upregulation of protein expression; and (4) no difference in HepG 2 cell proliferation. Our results suggest that TAM can induce hepatocyte steatosis in vitro and that the enhancement of fatty acid synthesis through the upregulations of SREBP-1c and its downstream target genes (FAS, ACC and SCD) may be the key mechanism of TAM-induced hepatocyte steatosis.
Keywords: tamoxifen; HepG 2 cells; non-alcoholic fatty liver disease; triglyceride
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MDPI and ACS Style

Zhao, F.; Xie, P.; Jiang, J.; Zhang, L.; An, W.; Zhan, Y. The Effect and Mechanism of Tamoxifen-Induced Hepatocyte Steatosis in Vitro. Int. J. Mol. Sci. 2014, 15, 4019-4030.

AMA Style

Zhao F, Xie P, Jiang J, Zhang L, An W, Zhan Y. The Effect and Mechanism of Tamoxifen-Induced Hepatocyte Steatosis in Vitro. International Journal of Molecular Sciences. 2014; 15(3):4019-4030.

Chicago/Turabian Style

Zhao, Fei; Xie, Ping; Jiang, Jiali; Zhang, Lingqiang; An, Wei; Zhan, Yutao. 2014. "The Effect and Mechanism of Tamoxifen-Induced Hepatocyte Steatosis in Vitro." Int. J. Mol. Sci. 15, no. 3: 4019-4030.

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