Eupalinolide J Inhibits Cancer Metastasis by Promoting STAT3 Ubiquitin-Dependent Degradation

Abstract

Eupalinolide J (EJ) is an active component from Eupatorium lindleyanum DC. (EL), which was reported to have good antitumor activity via STAT3 and Akt signaling pathways. In this study, we identified Eupalinolide J (EJ) as a potential anti-cancer metastatic agent by target prediction and molecular docking technique screening. Follow-up experiments demonstrated that EJ exhibited a good inhibitory effect on cancer cell metastasis both in vitro and in vivo, and could effectively reduce the expression of STAT3, MMP-2, and MMP-9 proteins in cells, while the knockdown of STAT3 could weaken the inhibitory effect of EJ on cancer cell metastasis. Further molecular biology experiments revealed that EJ promoted STAT3 ubiquitin-dependent degradation, and thus, downregulated the expression of the metastasis-related genes MMP-2 and MMP-9. In conclusion, our study revealed that EJ, a sesquiterpene lactone from EL, could act as a STAT3 degradation agent to inhibit cancer cell metastasis and is expected to be applied in cancer therapy.