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  • NS5ABP37 inhibits liver cancer by impeding lipogenesis and cholesterogenesis.

NS5ABP37 inhibits liver cancer by impeding lipogenesis and cholesterogenesis.

Cancer science (2016-11-20)
Shenghu Feng, Ming Han, Li Zhou, Qi Wang, Zhongshu Li, Yaru Li, Hongping Lu, Ting Liu, Yanhua Ma, Shunai Liu, Jun Cheng
ABSTRACT

The molecular mechanism underlying non-alcoholic fatty liver disease progression to hepatocellular carcinoma (HCC) remains unknown. In this study, immunohistochemistry staining results showed that NS5ABP37 protein, which is in a state of lower expression in tumor tissues, decreased with increasing degree of HCC malignancy. Two cell models, HepG2 and L02, were used to analyze the mechanism between NS5ABP37 and HCC. In agreement, NS5ABP37 protein overexpression significantly suppressed cell proliferation, caused G1 /S cell cycle arrest, and induced apoptosis by increasing caspase-3/7 activity and cleaved caspase-3 levels. In addition, NS5ABP37 overexpression resulted in decreased intracellular triglyceride and total cholesterol contents, with level reduction in sterol regulatory element-binding proteins (SREBPs) and downstream effectors. Furthermore, NS5ABP37 overexpression decreased SREBP1c and SREBP2 levels by reducing their respective promoters. Finally, reactive oxygen species levels and endoplasmic reticulum stress were both induced by NS5ABP37 overexpression. These findings together indicate that NS5ABP37 inhibits cancer cell proliferation and promotes apoptosis, by altering SREBP-dependent lipogenesis and cholesterogenesis in HepG2 and L02 cells and inducing oxidative stress and endoplasmic reticulum stress.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Adipogenesis Kit, sufficient for 100 colorimetric or fluorometric tests
Sigma-Aldrich
Oil Red O, certified by the Biological Stain Commission