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

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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.

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Abbreviations

GPX4:

Glutathione peroxidase 4

ROS:

Reactive oxygen species

RCD:

Regulated cell death

γ-GCS:

γ-Glutamylcysteine synthetase

TFR1:

Transferrin receptor 1

DMT1:

Divalent metal transporter 1

IREB2:

Iron response element binding protein 2

CDKN1A:

Cyclin-dependent kinase inhibitor

ALOX15:

Arachidonate 15-lipoxygenase

DPP4:

Dipeptidyl peptidase 4

NRF2:

Nuclear factor erythroid 2 related factors 2

Keap:

Kelch-like ECH-associated protein 1

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Authors and Affiliations

  1. Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran

    Shiva Rahimipour Anaraki & Reza Barati

  2. Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran

    Payam Farzami

  3. Faculty of Pharmacy, Kerman University of Medical Sciences, Kerman, Iran

    Seyed Soheil Hosseini Nasab & Ali Kousari

  4. Infectious Diseases and Tropical Medicine Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran

    Andarz Fazlollahpour Naghibi

  5. Oncopathology Research Center, Iran University of Medical Sciences, Tehran, Iran

    Mahdieh Shariat Zadeh & Seyed Reza Taha

  6. Faculty of Medicine, Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

    Ansar Karimian & Bahman Yousefi

  7. Department of Biochemistry, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran

    Mohsen Nabi-Afjadi

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  1. Shiva Rahimipour Anaraki
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The core of the study came from MN-A and BY. SHR-A, PF, SSHN, AK, AFN, AFZ, MSZ, RB, SRT, AK, and MN-A wrote the manuscript. Final editing was done by MN-A, and BY supervised the manuscript. The authors confirm that no paper mill and artificial intelligence was used.

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Correspondence to Mohsen Nabi-Afjadi or Bahman Yousefi.

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Rahimipour Anaraki, S., Farzami, P., Hosseini Nasab, S.S. et al. Natural products and the balancing act of autophagy-dependent/independent ferroptosis in cancer therapy. Naunyn-Schmiedeberg's Arch Pharmacol 397, 2531–2549 (2024). https://doi.org/10.1007/s00210-023-02782-1

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