Daidzin inhibits hepatocellular carcinoma survival by interfering with the glycolytic/gluconeogenic pathway through downregulation of TPI1.

Abstract

Daidzin (DDZ) is a natural brassin-like compound extracted from the soybean, and has been found to have therapeutic potential against tumors in recent years. This study investigates the therapeutic effect of DDZ on hepatocellular carcinoma cells and elucidates the possible mechanisms of action. The viability of HCCLM3 and Hep3B cells was detected by MTT assay. Western blots and qPCR were used to detect the protein and mRNA levels of proliferation and apoptosis related genes. Gas chromatography-mass spectrometry (GC-MS) was used for metabolome analysis. In vivo antitumor effects were assessed in nude mice engrafted with HCC cell lines. Our results show that DDZ treatment dose-dependently inhibited cell viability, migration, and survival. The expressions of CDK1, BCL2, MYC, and survivin were reduced, while the expressions of BAX and PARP were increased in DDZ treated cells. The differentially expressed metabolites detected in DDZ treated cultures are associated with glycolysis/gluconeogenesis pathways. Bioinformatic analysis identified TPI1, a gene in the glycolysis pathway with prognostic value for hepatocellular carcinoma (HCC), and DDZ treatment downregulated this gene. In vivo experiments show that DDZ significantly reduced the tumor volume and weight, and inhibited Ki67 expression within tumors. This study shows that DDZ interfered with the survival and migration of hepatocellular carcinoma cells, likely via TPI1 and the gluconeogenesis pathway.

• Authors: Lanqing Li, Haiying Xu, Linghang Qu, Kang Xu, Xianqiong Liu
• Journal: BioFactors (Oxford, England) (Biofactors) Vol. 48 Issue 4 Pg. 883-896 (Jul 2022) ISSN: 1872-8081 [Electronic] Netherlands
• PMID: 35118741 (Publication Type: Journal Article)
• Copyright: © 2022 International Union of Biochemistry and Molecular Biology.

Chemical References

• Isoflavones
• daidzin

Topics

• Animals
• Apoptosis
• Carcinoma, Hepatocellular (drug therapy, genetics, metabolism)
• Cell Line, Tumor
• Cell Proliferation
• Down-Regulation
• Gene Expression Regulation, Neoplastic
• Isoflavones
• Liver Neoplasms (drug therapy, genetics, metabolism)
• Mice
• Mice, Nude