The active components of Smilax china L. against cancer by interfering with the interactions among associated proteins

Abstract

In tumors, Heat shock protein HSP 90-alpha (Hsp90α) maintains the activity of over-activated or mutated signal transduction proteins and accelerates the malignant transformation of tumor cells. The extracellular Hsp90α interacts with client proteins resulting in promotion of tumor invasion and metastasis. This study investigated possible bioactive components of Smilax china L. and their effects on the interactions among tumor-associated proteins. We demonstrated that the protein Hsp90α, screened by combining transcriptome, proteomics and docking, could interact with the active compounds through microscale thermophoresis (MST), and Hsp90α could also interact with fatty acid synthase (FASN) and Vinculin. Meanwhile, scopolin could affect the interaction between Hsp90α and FASN. Animal experiments demonstrated that scopolin may have anticancer effect by affecting the stability of tumor-related proteins. Results showed that scopolin could interact with Hsp90α and inhibit the interactions between proteins, thereby against cancer.Practical applications.Smilax china L. has been reported to have an anti-tumor effect. This study shows that the bioactive ingredient scopolin from Smilax china L. can effectively inhibit the proliferation of hepatocellular carcinoma tumor cells, and can block the interaction between tumor-related protein Hsp90α and FASN. The results suggest that scopolin may be a potential cancer inhibitor that blocks the interactions of cancer-related proteins, which provides a potential basis for drug research and development for cancer that seriously puzzles human health.

Keywords

• Scopolin
• Microscale thermophoresis
• Hsp90α inhibitor
• Hsp90α/FASN pathway
• Hsp90α/Vinculin pathway