Centipeda minima extract exhibits anti-liver cancer effects via the ER stress/HMOX1/Fe2+/ROS pathway

Abstract

Background

Centipeda minima (CM), also known as Ebushicao, has been traditionally utilized in Chinese medicine over thousands of years to address rhinitis, nasal allergies, and cancers. However, the active compounds and mechanism of CM against liver cancer have not been elucidated.

Purpose

To reveal the anticancer effects and the molecular mechanism of CM against liver cancer.

Methods

Compounds from the ethanolic extract of CM (ECM) were identified using UPLC-MS/MS. Two graded doses of ECM were introduced via gavage into mice bearing HepG2 cells for 24 days to evaluate its in vivo antitumor effects. Three doses of ECM were added to the cells to evaluate its in vitro anticancer effects via colony-formation, cell cycle, apoptosis, wound healing, transwell, western blot, and Fe²⁺ and ROS detection assays. Network pharmacology and RNA sequencing were conducted to examine the mechanism by which ECM affects liver cancer.

Results

ECM significantly arrested the cell cycle at G2/M, induced apoptosis, and impeded invasion and cell migration in liver cancer. In addition, ECM restrained tumor growth without affecting mouse weight. Mechanistically, ECM upregulated HMOX1 expression via ER stress, leading to accumulation of Fe²⁺, ROS, and cell apoptosis. Moreover, ECM impeded cell migration and invasion via downregulating N-cadherin (N-cad) and upregulating E-cadherin (E-cad).

Conclusion

ECM might restrain liver cancer progression primarily through the ER stress/HMOX1/Fe²⁺/ROS pathway, presenting a possible therapeutic strategy for managing liver cancer.