Eupalinolide O

Nat Prod Res,2019 Feb;33(4):477-485.

Precise discovery of a STAT3 inhibitor from Eupatorium lindleyanum and evaluation of its activity of anti-triple-negative breast cancer.[Pubmed: 29086600]

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).
METHODS AND RESULTS:
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.
CONCLUSIONS:
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.

Bioorg. Med. Chem.,2011 Nov 1;19(21):6254-60.

Eupalinolide O, a novel sesquiterpene lactone from Eupatorium lindleyanum DC., induces cell cycle arrest and apoptosis in human MDA-MB-468 breast cancer cells.[Reference: WebLink]

Sesquiterpene lactones have been confirmed to have potential antitumor activity.
METHODS AND RESULTS:
Here, we demonstrated that Eupalinolide O (EO), a novel sesquiterpene lactone isolated from Eupatorium lindleyanum DC., showed significant anticancer activity against human MDA-MB-468 breast cancer cells. The cytotoxicity induced by EO was mediated by induction of apoptosis. Flow cytometric analysis demonstrated that EO treatment resulted in loss of the mitochondrial membrane potential in cancer cells which is regarded as a hallmark of apoptosis. Further study demonstrated that EO induced apoptotic cell death in the MDA-MB-468 cells through the activation of caspases. The effect of EO on the induction of apoptosis was significantly prevented by the treatment of pan-caspase inhibitor Z-VAD-FMK. We also found that EO treatment resulted in cell cycle arrest in the G2/M phase. The expression of cell cycle-related proteins (cyclin B1 and cdc2) was significantly decreased. Furthermore, the suppression of the Akt pathway in the MDA-MB-468 cells was observed.
CONCLUSIONS:
Collectively, EO suppressed the growth of the MDA-MB‑468 cells possibly by cell cycle arrest in the G2/M phase and the induction of caspase-dependent apoptosis. These results suggest that EO is a promising natural compound for breast cancer therapy.