Pomiferin Induces Antiproliferative and Pro-Death Effects in High-Risk Neuroblastoma Cells by Modulating Multiple...

Area of Science:

• Oncology
• Pharmacology
• Natural Products

Background:

• Chemotherapy resistance in high-risk neuroblastoma (NB) is a major clinical challenge.
• Natural compounds like isoflavones from Osage orange (Maclura pomifera) exhibit anticancer properties.
• Investigating novel agents to overcome drug resistance in NB is crucial.

Purpose of the Study:

• To evaluate the antiproliferative and cytotoxic effects of osajin and pomiferin in neuroblastoma cell lines.
• To determine the mechanisms of cell death induced by these natural compounds.
• To explore their potential in overcoming chemotherapy resistance in NB.

Main Methods:

• Assessed antiproliferative and cytotoxic effects of osajin and pomiferin on NB cell lines.
• Quantified apoptosis induction using various assays.
• Investigated ferroptosis, pyroptosis, and necroptosis pathways.
• Analyzed GPX4 inhibition, lipid peroxidation, autophagic machinery, and gasdermin E cleavage.

Main Results:

• Both osajin and pomiferin reduced NB cell proliferation and induced cytotoxicity, with pomiferin being more potent (lower IC50).
• Pomiferin dose-dependently increased apoptosis and activated multiple cell death pathways.
• Pomiferin induced ferroptosis via GPX4 inhibition and lipid peroxidation, impaired autophagy, and triggered pyroptosis in MYCN-amplified cells.
• Necroptosis was not observed.

Conclusions:

• Pomiferin demonstrates significant antiproliferative and cytotoxic activity against high-risk neuroblastoma cells.
• Pomiferin effectively induces multiple cell death pathways, including apoptosis, ferroptosis, and pyroptosis.
• Pomiferin represents a potential therapeutic strategy to overcome conventional chemotherapy resistance in neuroblastoma.