Related Experiment Video
Updated: Aug 13, 2025
Author Spotlight: Tracing the Ferroptotic Signatures and Cell Death Dynamics in Medulloblastoma for Advanced Therapeutics
Published on: March 15, 2024
Review and Chemoinformatic Analysis of Ferroptosis Modulators with a Focus on Natural Plant Products
Višnja Stepanić1, Marta Kučerová-Chlupáčová2
1Laboratory for Machine Learning and Knowledge Representation, Ruđer Bošković Institute, Bijenička 54, 10000 Zagreb, Croatia.
Abstract:
Ferroptosis is a regular cell death pathway that has been proposed as a suitable therapeutic target in cancer and neurodegenerative diseases. Since its definition in 2012, a few hundred ferroptosis modulators have been reported. Based on a literature search, we collected a set of diverse ferroptosis modulators and analyzed them in terms of their structural features and physicochemical and drug-likeness properties. Ferroptosis modulators are mostly natural products or semisynthetic derivatives. In this review, we focused on the abundant subgroup of polyphenolic modulators, primarily phenylpropanoids. Many natural polyphenolic antioxidants have antiferroptotic activities acting through at least one of the following effects: ROS scavenging and/or iron chelation activities, increased GPX4 and NRF2 expression, and LOX inhibition. Some polyphenols are described as ferroptosis inducers acting through the generation of ROS, intracellular accumulation of iron (II), or the inhibition of GPX4. However, some molecules have a dual mode of action depending on the cell type (cancer versus neural cells) and the (micro)environment. The latter enables their successful use (e.g., apigenin, resveratrol, curcumin, and EGCG) in rationally designed, multifunctional nanoparticles that selectively target cancer cells through ferroptosis induction.
Insights
Ferroptosis modulators, particularly polyphenols, show dual roles in cancer and neurodegenerative diseases. Their properties are analyzed for therapeutic potential, with some used in targeted nanoparticles for cancer therapy.
Area of Science:
- Biochemistry
- Pharmacology
- Cell Biology
Background:
- Ferroptosis, a regulated cell death pathway, is a promising therapeutic target for cancer and neurodegenerative diseases.
- Hundreds of ferroptosis modulators have been identified since 2012, with many being natural products or semi-synthetic derivatives.
Purpose of the Study:
- To analyze the structural, physicochemical, and drug-likeness properties of diverse ferroptosis modulators.
- To focus on polyphenolic modulators, particularly phenylpropanoids, and their mechanisms of action.
Main Methods:
- Literature search to collect and analyze ferroptosis modulators.
- Evaluation of structural features, physicochemical properties, and drug-likeness.
- Categorization of modulators based on their effects (induction or inhibition of ferroptosis).
Main Results:
- Polyphenolic antioxidants often exhibit antiferroptotic activity via ROS scavenging, iron chelation, or boosting GPX4/NRF2 expression.
- Some polyphenols can induce ferroptosis through ROS generation, iron accumulation, or GPX4 inhibition.
- Certain molecules display dual modes of action, varying with cell type and environment.
Conclusions:
- Polyphenolic ferroptosis modulators possess diverse mechanisms, including dual roles.
- Compounds like apigenin, resveratrol, curcumin, and EGCG can be utilized in multifunctional nanoparticles for targeted cancer therapy via ferroptosis induction.
More Related Videos
11:44Cellular Membrane Affinity Chromatography Columns to Identify Specialized Plant Metabolites Interacting with Immobilized Tropomyosin Kinase Receptor B
Published on: January 19, 2022
07:07Synthetic Methodology for Asymmetric Ferrocene Derived Bio-conjugate Systems via Solid Phase Resin-based Methodology
Published on: March 12, 2015