PUBLICATION
The lipid homeostasis regulation study of arenobufagin in zebrafish HepG2 xenograft model and HepG2 cells using integrated lipidomics-proteomics approach
- Authors
- Zhao, L.J., Zhao, H.Y., Wei, X.L., Guo, F.F., Wei, J.Y., Wang, H.J., Yang, J., Yang, Z.G., Si, N., Bian, B.L.
- ID
- ZDB-PUB-200519-7
- Date
- 2020
- Source
- Journal of ethnopharmacology 260: 112943 (Journal)
- Registered Authors
- Keywords
- Amino acid, Anti-hepatoma, Arenobufagin, Lipid homeostasis, Lipidomics, Proteomics
- MeSH Terms
-
- Animals
- Antineoplastic Agents/pharmacology*
- Apoptosis/drug effects
- Apoptosis Regulatory Proteins/metabolism
- Autophagy/drug effects
- Autophagy-Related Proteins/metabolism
- Bufanolides/pharmacology*
- Carcinoma, Hepatocellular/drug therapy*
- Carcinoma, Hepatocellular/genetics
- Carcinoma, Hepatocellular/metabolism
- Carcinoma, Hepatocellular/pathology
- Gene Expression Regulation, Neoplastic
- Hep G2 Cells
- Humans
- Lipid Metabolism/drug effects*
- Lipid Metabolism/genetics
- Lipidomics*
- Liver Neoplasms/drug therapy*
- Liver Neoplasms/genetics
- Liver Neoplasms/metabolism
- Liver Neoplasms/pathology
- Protein Interaction Maps
- Proteomics*
- Signal Transduction
- Xenograft Model Antitumor Assays
- Zebrafish
- PubMed
- 32422359 Full text @ J. Ethnopharmacol.
Citation
Zhao, L.J., Zhao, H.Y., Wei, X.L., Guo, F.F., Wei, J.Y., Wang, H.J., Yang, J., Yang, Z.G., Si, N., Bian, B.L. (2020) The lipid homeostasis regulation study of arenobufagin in zebrafish HepG2 xenograft model and HepG2 cells using integrated lipidomics-proteomics approach. Journal of ethnopharmacology. 260:112943.
Abstract
Ethnopharmacological relevance Arenobufagin (ArBu) is an important anti-tumor ingredient of Chan'su which has long been used as traditional Chinese medicine in clinic for tumor therapy in China.
Aim of the study The purpose of our study is to investigate the lipid homeostasis regulation effects of ArBu on zebrafish model of liver cancer and hepatoma cells, and to provide a reference for further clarifying its active mechanisms.
Materials and methods The zebrafish xenograft model was established by injecting HepG2 cells stained with CM-Dil red fluorescent dye. Both the xenograft model and HepG2 cells were used to evaluate the anti-hepatoma activity of ArBu. High performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was the main method to study lipidomics, proteomics and the semiquantification of endogenous metabolites. Bioinformatics was used as an assistant tool to further explore the antitumor mechanism of ArBu.
Results The lipidomics analysis revealed that ArBu caused differential lipids changes in a dose-dependent manner, including PCs, PEs, TGs, SMs, DGs, Cer and PA. PCs, PEs, SMs and TGs were markedly altered in both two models. The influence of glycerophospholipid metabolism was the major and commonly affected pathway. Notably, DGs and Cer were significantly changed only in HepG2 cells. Furthermore, the proteomics research in HepG2 cells fished the target proteins related to lipid homeostasis abnormalities and tumor suppression. ArBu reduced the expression of 65 differential proteins associated with the lipid metabolism, apoptosis and autophagy, such as LCLAT1, STAT3, TSPO and RPS27. Meanwhile, 7 amino acids of 29 determined metabolites were significantly changed, including tyrosine, glutamate, glutamine, leucine, threonine, arginine and isoleucine.
Conclusion ArBu has a significant anti-hepatoma effect in vitro and a therapeutic effect on zebrafish xenograft model. It regulated the lipid homeostasis. Activated SM synthase and arginine deiminase, inhibited sphingomyelinase, amino acid supply and JAK-STAT3 signaling pathway, and the affected glycerophospholipid metabolism might explain these results.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping