Natural products and the balancing act of autophagy-dependent/independent ferroptosis in cancer therapy

Naunyn Schmiedebergs Arch Pharmacol. 2024 May;397(5):2531-2549. doi: 10.1007/s00210-023-02782-1. Epub 2023 Oct 25.

Abstract

The control of biological cell death is essential for the body's appropriate growth. The resistance of cells to the apoptotic process presents a new difficulty in the treatment of cancer. To combat cancer cells, researchers are working to find new apoptotic pathways and components to activate. One of the processes of regulated cell death (RCD) is referred to as ferroptosis marked by a decline in the activity of lipid glutathione peroxidase 4 (GPX4) after the buildup of reactive oxygen species (ROS). Since lipid peroxidation is a crucial component of ferroptosis and is required for its start, numerous medicines have been studied, particularly for the treatment of cancer. In this context, autophagy is an additional form of RCD that can govern ferroptosis through shared signaling pathways/factors involved in both mechanisms. In this review, we will explore the molecular mechanisms underlying ferroptosis and its association with autophagy, to gain fresh insights into their interplay in cancer advancement, and the potential of natural products for its treatment.

Keywords: Apoptosis; Autophagy; Ferroptosis; Lipid glutathione peroxidase; Natural products.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Autophagy* / drug effects
  • Biological Products* / pharmacology
  • Biological Products* / therapeutic use
  • Ferroptosis* / drug effects
  • Ferroptosis* / physiology
  • Humans
  • Neoplasms* / drug therapy
  • Neoplasms* / metabolism
  • Neoplasms* / pathology
  • Reactive Oxygen Species / metabolism
  • Signal Transduction / drug effects

Substances

  • Biological Products
  • Reactive Oxygen Species
  • Antineoplastic Agents