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Actinidia chinensis Planch root extract inhibits cholesterol metabolism in hepatocellular carcinoma through upregulation of PCSK9
- Source :
- Oncotarget
- Publication Year :
- 2017
- Publisher :
- Impact Journals, LLC, 2017.
-
Abstract
- // Mingyan He 1, * , Jiayun Hou 2, * , Lingyan Wang 2, * , Minghuan Zheng 2 , Tingting Fang 1 , Xiangdong Wang 2 and Jinglin Xia 1, 3 1 Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China 2 Clinical Science Institute, Zhongshan Hospital, Fudan University, Shanghai, China 3 Minhang Hospital, Fudan University, Shanghai, China * These authors have contributed equally to this work Correspondence to: Jinglin Xia, email: xiajinglin@fudan.edu.cn Xiangdong Wang, email: xianagdong.wang@clintransmed.org Keywords: hepatocellular carcinoma, root of Actinidia chinensis, PCSK9, cholesterol metabolism Received: September 09, 2016 Accepted: January 16, 2017 Published: February 02, 2017 ABSTRACT Actinidia chinensis Planch root extract (acRoots) is a traditional Chinese medicine with anti-tumor efficacy. To investigate the mechanisms responsible for this activity, we examined the effects of acRoots on cholesterol metabolism in hepatocellular carcinoma (HCC). mRNA chip analysis was used to identify the metabolic genes regulated by acRoots. The effects of acRoots on cholesterol synthesis and uptake were evaluated by measuring intracellular cholesterol levels and 3,3’-dioctadecylindocarbocyanine-labeled low-density lipoprotein (Dil-LDL) uptake. Expression of metabolic genes was analyzed using quantitative reverse transcription PCR, western blotting, and flow cytometry. acRoots reduced the viability of LM3 and HepG2 cells at 5 mg/mL and HL-7702 cells at 30 mg/mL. Gene expression profiling revealed that treatment with acRoots altered expression of genes involved in immune responses, inflammation, proliferation, cell cycle control, and metabolism. We also confirmed that acRoots enhances expression of PCSK9 , which is important for cholesterol metabolism. This resulted in decreased LDL receptor expression, inhibition of LDL uptake by LM3 cells, decreased total intracellular cholesterol, and reduced proliferation. These effects were promoted by PCSK9 overexpression and rescued by PCSK9 knockdown. Our data demonstrate that acRoots is a novel anti-tumor agent that inhibits cholesterol metabolism though a PCSK9 -mediated signaling pathway.
- Subjects :
- 0301 basic medicine
Carcinoma, Hepatocellular
Actinidia chinensis
Receptor expression
Actinidia
Pharmacology
Models, Biological
Plant Roots
PCSK9
03 medical and health sciences
0302 clinical medicine
Cell Line, Tumor
medicine
Humans
Cell Proliferation
Gene knockdown
biology
Plant Extracts
Gene Expression Profiling
Liver Neoplasms
Intracellular Signaling Peptides and Proteins
Membrane Proteins
root of Actinidia chinensis
hepatocellular carcinoma
Lipid Metabolism
biology.organism_classification
medicine.disease
Gene Expression Regulation, Neoplastic
Gene expression profiling
Cholesterol
030104 developmental biology
Oncology
Biochemistry
030220 oncology & carcinogenesis
Hepatocellular carcinoma
cholesterol metabolism
Proprotein Convertase 9
Signal transduction
Metabolic Networks and Pathways
Signal Transduction
Research Paper
Lipoprotein
Subjects
Details
- ISSN :
- 19492553
- Volume :
- 8
- Database :
- OpenAIRE
- Journal :
- Oncotarget
- Accession number :
- edsair.doi.dedup.....22b8ad9b879fd7de65630ea082775cbb