Molecular mechanisms of ferroptosis and its antitumor applications in natural products

Abstract

Ferroptosis, an iron-dependent form of regulated cell death, results in lipid peroxidation of polyunsaturated fatty acids in the cell membrane, which is catalyzed by iron ions and accumulated to lethal levels. It is mechanistically distinct from other forms of cell death, such as apoptosis, pyroptosis, and necroptosis, so it may address the problem of cancer resistance to apoptosis and provide new therapeutic strategies for cancer treatment, which has been intensively studied over the past few years. Notably, considerable advances have been made in the antitumor research of natural products due to their multitargets and few side effects. According to research, natural products can also induce ferroptosis in cancer therapies. In this review we summarize the molecular mechanisms of ferroptosis, introduce the key regulatory genes of ferroptosis, and discuss the progress of natural product research in the field of ferroptosis to provide theoretical guidance for research on natural product-induced ferroptosis in tumors.

The mechanism by which piR-000699 targets SLC39A14 regulates ferroptosis in aging myocardial ischemia/reperfusion injury

“…Ferroptosis is an innovative form of programmed cell death that relies on iron and iron deposition from apoptosis and necrosis [21,22]. Ferroptosis can be activated by iron overload or by inactivation of GPX4, the major endogenous mechanism for preventing peroxidation 7-9, which converts potentially toxic lipid hydroperoxides into nontoxic lipid alcohols 10 [23].…”

Caffeic acid phenethyl ester promotes oxaliplatin sensitization in colon cancer by inhibiting autophagy

“…Selecting appropriate natural products as chemotherapy adjuvants can greatly reduce the side effects of chemotherapeutic drugs and improve their antitumor effects. As the main active ingredient of propolis, CAPE targets multiple signaling pathways to inhibit cancer progression 34 , 35 . Currently, the underlying mechanisms of CAPE in colon cancer remain unclear.…”

Ferroptosis: a new mechanism of traditional Chinese medicine for cancer treatment

“…Long-chain PUFAs such as arachidonic acid (AA) and adrenic acid (AdA) exist primarily in their free forms. The derivatized AA-CoA or AdA-CoA is combined with CoA through ACSL4, and subsequently subjected to additional modifications by LPCAT3 to generate membrane phosphatidylethanolamine (AA-PE or AdA-PE) ( Yu et al, 2023 ). PE-AA is a PUFA that can be catalyzed by LOX15 and Fe 2+ to generate oxidized phospholipid ox-PE, thereby participating in the initiation of ferroptosis ( Shimada et al, 2016 ).…”

“…The release of DAMPs by various forms of cell death can result in the maturation of dendritic cells, reciprocal activation of CD8 + T cells, generation of IFN-γ, and the establishment of a positive loop between the immune and inflammatory responses ( Yu et al, 2023 ). Phagocytosis of tumor cells undergoing ferroptosis is triggered by three important DAMPs in bone marrow-derived dendritic cells: calreticulin (CRT), high-mobility group protein B1 (HMGB1), and adenosine triphosphate (ATP) ( Turubanova et al, 2019 ).…”