Abstract

Excess iron is associated with carcinogenesis. Ferric nitrilotriacetate-induced renal cancers in wild-type rats reveal similar genetic alterations to those in humans. Ferroptosis may be defined as a form of regulated necrosis, characterized by lipid peroxidation through high iron/sulfur(antioxidants) ratio. Considering that cancer cells in general retain more catalytic Fe(II) than non-tumorous cells, many iron-induced carcinogenesis models, including asbestos-induced mesothelioma, suggest that cancer is a state of iron addiction with ferroptosis-resistance. Non-thermal plasma (NTP) is a novel physical technique that emits abundant electrons, leading to a variety of ROS products by reaction with atmospheric oxygen. Exposure of NTP to biomolecules, cells or tissues causes oxidative stress in situ, resulting in DNA breaks and lipid peroxidation products, such as HNE. We found that NTP exposure is highly dependent on Fe(II) in situ, causing cancer cell-specific ferroptosis, which was associated with autophagy activation and lysosome genesis. Thus, we discuss the role of phlebotomy for cancer prevention and the use of NTP as a new cancer therapy.

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