Precise discovery of a STAT3 inhibitor from Eupatorium lindleyanum and evaluation of its activity of anti-triple-negative breast cancer

Abstract

Michael reaction acceptors (MRAs) are a class of active compounds. There is a great prospect to screen STAT3 inhibitors from Eupatorium lindleyanum, furthermore, to discover lead compounds for anti-triple-negative breast cancer (TNBC). In this study, glutathione (GSH) was employed, and a UPLC-MS screening method was developed to discover MRAs. We screened MRAs which can inhibit STAT3 using a STAT3-dependent reporter system. Six sesquiterpene lactones, including a new compound Eupalinolide O (1), together with five known compounds, Eupalinolide I (2), Eupalinolide K (3), Eupalinolide H (4), Eupalinolide J (5) and Eupalinolide G (6) were isolated. Eupalinolide J was identified as MRA that decreased luciferase activity of STAT3. Preliminary activity assessment showed that Eupalinolide J could inhibit the viability of TNBC cell lines. We demonstrated that Eupalinolide J, which is a natural typical MRA, has a notable inhibition of STAT3 activity and a potential cytotoxic activity against TNBC cell lines.

Keywords:

• Sesquiterpene lactone
• STAT3 inhibitor
• precise discovery
• triple-negative breast cancer