Ferroptosis: Potential opportunities for natural products in cancer therapy

Abstract

Cancer cells often exhibit defects in the execution of cell death, resulting in poor clinical outcomes for patients with many cancer types. Ferroptosis is a newly discovered form of programmed cell death characterized by intracellular iron overload and lipid peroxidation in the cell membrane. Increasing evidence suggests that ferroptosis is closely associated with a wide variety of physiological and pathological processes, particularly in cancer. Notably, various bioactive natural products have been shown to induce the initiation and execution of ferroptosis in cancer cells, thereby exerting anticancer effects. In this review, we summarize the core regulatory mechanisms of ferroptosis and the multifaceted roles of ferroptosis in cancer. Importantly, we focus on natural products that regulate ferroptosis in cancer cells, such as terpenoids, polyphenols, alkaloids, steroids, quinones, and polysaccharides. The clinical efficacy, adverse effects, and drug–drug interactions of these natural products need to be evaluated in further high‐quality studies to accelerate their application in cancer treatment.

Ferroptosis in Cancer Therapy: Mechanisms, Small Molecule Inducers, and Novel Approaches

“…323 With the increasing research on ferroptosis, more and more natural products have been found to have ferroptosisinducing effects. 324 Although these natural products themselves have limited effects in inducing ferroptosis in tumor cells, their discovery has provided lead compounds for the development of ferroptosis inducers. For example, compound 31, synthesized by combining the core of the natural product indirubin with the active fragment of a GPX4 covalent inhibitor via a linker, effectively inhibited human colon cancer cells.…”

Targeting ferroptosis regulators by natural products in colorectal cancer

“…Natural products often play a role in adjusting cellular equilibrium, interacting with signaling pathways related to both cell death and survival, and displaying antioxidant and anti-inflammatory characteristics. The historical utilization of certain natural products in traditional medicine, coupled with clinical evidence supporting their safety and effectiveness in treating cancers, lend credibility to their potential as agents inducing ferroptosis ( Nie et al, 2023 ).…”