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

  • Nat Prod Res. 2019 Feb;33(4):477-485. doi: 10.1080/14786419.2017.1396596.
Bo Yang  1 ,  Jia Wei Shen  2 ,  Dong Heng Zhou  1 ,  Ya Ping Zhao  1  3 ,  Wei Qian Wang  1 ,  Ying Zhu  1 ,  Hua Jun Zhao  1
Affiliations
  • 1. a College of Pharmaceutical Sciences , Zhejiang Chinese Medical University , Hangzhou , P. R. China.
  • 2. b School of Medicine , Hangzhou Normal University , Hangzhou , P. R. China.
  • 3. c Department of Pharmaceutics , Shaoxing Hospital of Traditional Chinese Medicine , Shaoxing , P. R. China.
PMID: 29086600 DOI: 10.1080/14786419.2017.1396596
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
STAT3 inhibitor; Sesquiterpene lactone; precise discovery; triple-negative breast cancer.
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