Recent trends in emerging strategies for ferroptosis-based cancer therapy

Abstract

Ferroptosis, an iron-dependent mode of regulated cell death, is induced by lipid peroxidation, whose occurrence and execution are primarily controlled by metabolism of iron, lipids, amino acids and glutathione.

Deferasirox Targeting Ferroptosis Synergistically Ameliorates Myocardial Ischemia Reperfusion Injury in Conjunction With Cyclosporine A

“…Damaged mitochondria (as a feature of ferroptosis) were defined as mitochondria with reduced mitochondrial cristae or ruptured outer mitochondrial membranes as reported previously. 35 The damaged mitochondria were quantified relative to the total number of mitochondria.…”

Ferroptosis and its current progress in gastric cancer

“…The cell nucleus in ferroptotic cells remains intact, setting it apart from apoptosis ( Rishi et al, 2021 ). Ferroptosis plays a widespread role in regulating various pathophysiological processes in the human body, including tumor cell death, neurodegenerative diseases, tissue ischemia/reperfusion injury, T-cell immunity, and more ( Xie et al, 2016 ; Yu et al, 2023 ). Within ferroptotic cells, the excessive accumulation of reactive oxygen species (ROS) and lipid peroxides results in the oxidative destruction of phospholipid molecules containing polyunsaturated fatty acids (PUFAs) in cell membranes and organelle membranes.…”

“…Within ferroptotic cells, the excessive accumulation of reactive oxygen species (ROS) and lipid peroxides results in the oxidative destruction of phospholipid molecules containing polyunsaturated fatty acids (PUFAs) in cell membranes and organelle membranes. This, in turn, leads to membrane damage ( Hassannia et al, 2019 ; Yu et al, 2023 ). Research by Riegman et al confirms that the cellular iron death signal initially spreads in a wave-like manner within a cell population, subsequently leading to cell swelling downstream in the signaling cascade, ultimately culminating in cell rupture mediated by the plasma membrane pores ( Riegman et al, 2020 ; Rishi et al, 2021 ).…”

Marine Alkaloid Lepadins E and H Induce Ferroptosis for Cancer Chemotherapy

“…Class I includes erastin, the prototype of the ferroptosis inducer; sorafenib, , and sulfasalazine, which inhibit the cystine/glutamate antiporter (xCT) system. Class II includes RSL3, DPI7, and DPI10, which directly inactivate glutathione peroxidase 4 (GPX4). , Class III consists of FIN56, which induces ferroptosis through either promoting GPX4 degradation or depleting antioxidant coenzyme Q10 (CoQ10). , Class IV includes the organic peroxide FINO2, which triggers ferroptosis by oxidizing ferrous iron and indirectly inhibiting GPX4. ,, These organic ferroptosis inducers have played an important role in elucidating and establishing the molecular mechanisms of ferroptosis. ,, However, few of them are advanced to clinical trials/practices for cancer treatment due to unfavorable physiochemical properties. , Natural products with evolutionary advantages of physiochemical properties have been a main source of antitumor drugs , but are sparsely investigated as ferroptosis inducers. Herein, we report our discovery of marine alkaloid natural product lepadins E and H as a new class of ferroptosis inducers.…”

“…29,33,34 However, few of them are advanced to clinical trials/practices for cancer treatment due to unfavorable physiochemical properties. 35,36 Natural products with evolutionary advantages of physiochemical properties have been a main source of antitumor drugs 37,38 but are sparsely investigated as ferroptosis inducers. Herein, we report our discovery of marine alkaloid natural product lepadins E and H as a new class of ferroptosis inducers.…”