Eupalinolide B inhibits hepatic carcinoma by inducing ferroptosis and ROS-ER-JNK pathway

Area of Science:

• Oncology
• Pharmacology
• Molecular Biology

Background:

• Primary hepatic carcinoma presents a significant clinical challenge, with existing treatments like sorafenib being costly and variably effective.
• Eupalinolide B (EB), a compound from *Eupatorium lindleyanum* DC., is used clinically for chronic tracheitis, but its anti-cancer potential is unexplored.

Purpose of the Study:

• To investigate the anti-tumor effects of Eupalinolide B (EB) on primary hepatic carcinoma.
• To elucidate the molecular mechanisms underlying EB's action, including its impact on cell proliferation, migration, cell cycle, apoptosis, autophagy, and ferroptosis.

Main Methods:

• Tumor growth was assessed using xenograft and patient-derived xenograft (PDX) models.
• In vitro studies involved human hepatocarcinoma cell lines (SMMC-7721, HCCLM3) to analyze cell proliferation, migration, cell cycle, apoptosis, autophagy, and ferroptosis via flow cytometry, western blot, and electron microscopy.

Main Results:

• EB demonstrated significant anti-proliferative activity by inducing S phase cell cycle arrest.
• EB triggered ferroptosis, mediated by endoplasmic reticulum (ER) stress and HO-1 activation, leading to cancer cell death.
• EB inhibited cell migration through the ROS-ER-JNK signaling pathway, independent of ferroptosis.

Conclusions:

• Eupalinolide B (EB) exhibits potent anti-proliferative and anti-migratory effects in hepatic carcinoma models.
• EB represents a promising novel therapeutic candidate for primary hepatic carcinoma, acting via ER stress-induced ferroptosis and JNK signaling pathway modulation.