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J Agric Food Chem. 2017 Jul 26;65(29):5961-5972. doi: 10.1021/acs.jafc.7b02120. Epub 2017 Jul 11.

Astragalin Reduces Hexokinase 2 through Increasing miR-125b to Inhibit the Proliferation of Hepatocellular Carcinoma Cells in Vitro and in Vivo.

Li W1,2, Hao J1,2, Zhang L1,2, Cheng Z1,2, Deng X1,2, Shu G1,2.

Author information

1
School of Pharmaceutical Sciences, South-Central University for Nationalities , Wuhan, China 430074.
2
National Demonstration Center for Experimental Ethnopharmacology Education, South-Central University for Nationalities , Wuhan, China 430074.

Abstract

Astragalin (ASG) can be found in a variety of food components. ASG exhibits cytotoxic effects on several different types of malignant cells. However, its effects on hepatocellular carcinoma (HCC) cells and the underlying molecular mechanisms have remained to be fully elucidated. Here, we revealed that ASG remarkably suppressed the proliferation of HCC cells. In HCC cells, ASG inhibited glucose glycolysis and promoted oxidative phosphorylation, resulting in a surge of reactive oxygen species (ROS). Mechanistically, ASG suppressed the expression of hexokinase 2 (HK2). This event was indispensible for ASG-mediated metabolic reprogramming, ROS accumulation, and subsequent growth arrest. Our further investigations unveiled that ASG repressed HK2 expression via increasing miR-125b. In vivo experiments showed that gavage of ASG decreased the proliferation of Huh-7 HCC xenografts in nude mice and inhibited the growth of transplanted H22 HCC cells in Kunming mice. Declined HCC tumor growth in vivo was associated with boosted miR-125b and reduced expression of HK2 in tumor tissues. Collectively, our results demonstrated that ASG is able to suppress the proliferation of HCC cells both in vitro and in vivo. Inhibition of HK2 through upregulating miR-125b and subsequent metabolic reprogramming is implicated in the antiproliferative effects of ASG on HCC cells.

KEYWORDS:

MiR-125b; astragalin; hepatocellular carcinoma; hexokinase 2; reactive oxygen species

PMID:
28654261
DOI:
10.1021/acs.jafc.7b02120
[Indexed for MEDLINE]

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