Natural Product-Induced Ferroptosis to Overcome Therapy Resistance in Aggressive Cancers

Ferroptosis as an emerging control for cell death: ferroptosis was introduced as an advanced version of regulated cell death that is defined by iron-dependent lipid peroxidation and redox imbalance, providing a candidate for anticancer medicine because of the possibility to achieve reduction of cancer resistance with conventional therapeutic agents. Recent findings demonstrate that natural products are a prospective rich source of ferroptosis regulators through their structural variety and intrinsic redox activity. In this perspective, we present a brief overview of recent developments (from 2026 to 2021) in natural product-induced ferroptosis and their translation into cancer treatments. Ferroptosis has been initiated via glutathione depletion, glutathione peroxidase 4 inhibition, iron accumulation, and generation of reactive oxygen species by natural compounds, such as polyphenols, alkaloids, terpenoids, and quinones. Several natural products show remarkable susceptibility to ferroptotic vulnerabilities that can sensitize drug-resistant cancer cells to chemotherapy and radiotherapy. Moreover, the polypharmacological characteristic of natural scaffolds allows the simultaneous manipulation of interrelated metabolic and redox pathways, which enhances therapeutic efficacy. Nevertheless, bioavailability, selectivity, and mechanistic comprehension are still challenges for such interesting discoveries. Natural product-induced ferroptosis in general is an attractive and novel alternative for promoting novel anticancer therapeutic strategies.