ACSL3 and ACSL4, Distinct Roles in Ferroptosis and Cancers

Yang, Yufei; Zhu, Tong; Wang, Xu; Xiong, Fen; Hu, Zhangmin; Qiao, Xuehan; Yuan, Xiao; Wang, Deqiang

doi:10.3390/cancers14235896

Cited by 79 publications

(35 citation statements)

References 82 publications

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“…Ferroptosis contributed to the effect, as evidenced by i.a. decreased expression of SLC7A11 and GPX4 as well as of SCD1 (stearoyl-CoA desaturase 1) and ACSL3 (acyl-CoA synthetase long-chain family member 3), both governing lipid metabolism, the disturbance of which entails phospholipid peroxidation [ 153 , 154 ].…”

Section: Poisons and Toxicantsmentioning

confidence: 99%

Bioinorganic Modulators of Ferroptosis: A Review of Recent Findings

Bartos

Sikora

2023

IJMS

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Ferroptosis was first reported as a separate modality of regulated cell death in 2008 and distinguished under its current name in 2012 after it was first induced with erastin. In the following decade, multiple other chemical agents were researched for their pro- or anti-ferroptotic properties. Complex organic structures with numerous aromatic moieties make up the majority of this list. This review fills a more overlooked niche by gathering, outlining and setting out conclusions regarding less prominent cases of ferroptosis induced by bioinorganic compounds and reported on within the last few years. The article contains a short summary of the application of bioinorganic chemicals based on gallium, several chalcogens, transition metals and elements known as human toxicants used for the purpose of evoking ferroptotic cell death in vitro or in vivo. These are used in the form of free ions, salts, chelates, gaseous and solid oxides or nanoparticles. Knowledge of how exactly these modulators promote or inhibit ferroptosis could be beneficial in the context of future therapies aimed against cancer or neurodegenerative diseases, respectively.

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Section: Poisons and Toxicantsmentioning

confidence: 99%

Bioinorganic Modulators of Ferroptosis: A Review of Recent Findings

Bartos

Sikora

2023

IJMS

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“…59 By displacing PUFAs from PEs within the cell membrane, this competitive process protects cells against ferroptosis. 59,60 However, it should be noted that in the context of mice with acute lung injury, OA has been shown to induce ferroptosis. 61 This suggests that the control of ferroptosis mediated by MUFAs is contingent on the specific context in which it occurs.…”

Section: Lipid Peroxidation and Membrane Damagementioning

confidence: 99%

“…Mechanistically, ACSL3, in conjunction with stearoyl‐CoA desaturase (SCD), converts MUFAs into their corresponding acyl‐CoA esters, which competitively interact with PUFAs 59 . By displacing PUFAs from PEs within the cell membrane, this competitive process protects cells against ferroptosis 59,60 . However, it should be noted that in the context of mice with acute lung injury, OA has been shown to induce ferroptosis 61 .…”

Section: Mechanism and Regulation Of Ferroptosismentioning

confidence: 99%

Targeting ferroptosis in gastric cancer: Strategies and opportunities

Le,

Pan,

Zhang

et al. 2023

Immunological Reviews

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SummaryFerroptosis is a novel form of programmed cell death morphologically, genetically, and biochemically distinct from other cell death pathways and characterized by the accumulation of iron‐dependent lipid peroxides and oxidative damage. It is now understood that ferroptosis plays an essential role in various biological processes, especially in the metabolism of iron, lipids, and amino acids. Gastric cancer (GC) is a prevalent malignant tumor worldwide with low early diagnosis rates and high metastasis rates, accounting for its relatively poor prognosis. Although chemotherapy is commonly used to treat GC, drug resistance often leads to poor therapeutic outcomes. In the last several years, extensive research on ferroptosis has highlighted its significant potential in GC therapy, providing a promising strategy to address drug resistance associated with standard cancer therapies. In this review, we offer an extensive summary of the key regulatory factors related to the mechanisms underlying ferroptosis. Various inducers and inhibitors specifically targeting ferroptosis are uncovered. Additionally, we explore the prospective applications and outcomes of these agents in the field of GC therapy, emphasizing their capacity to improve the outcomes of this patient population.

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“…However, whether DNMT1 inhibits ferroptosis‐related genes by regulating methylation of ferroptosis‐related genes is unclear. Acyl‐CoA synthetase long‐chain familymember4 (ACSL4) belongs to long‐chain acyl‐coenzyme synthetase (ACSL) family and is activated during ferroptosis 19 . Moreover, oeanolic acid repressed cervical cancer cell proliferation by inducing ACSL4‐dependent ferroptosis 20 .…”

Section: Introductionmentioning

confidence: 99%

“…Acyl-CoA synthetase longchain familymember4 (ACSL4) belongs to long-chain acyl-coenzyme synthetase (ACSL) family and is activated during ferroptosis. 19 Moreover, oeanolic acid repressed cervical cancer cell proliferation by inducing ACSL4-dependent ferroptosis. 20 Besides, miR-670-3p inhibited ferroptosis of human glioblastoma cells via binding ACSL4.…”

mentioning

confidence: 99%

Polyphyllin I induces ferroptosis in castration‐resistant prostate cancer cells through the ERK/DNMT1/ACSL4 axis

Zou,

Chen,

et al. 2023

The Prostate

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BackgroundCastration‐resistant prostate cancer (CRPC) inevitably arises after androgen deprivation therapy (ADT). Therefore, there is an urgent need to search for novel treatment strategies for CRPC. Polyphyllin I (PPI), one of the steroidal saponins in paris polyphylla, has been shown to have an anticancer effect. This study investigated the role and mechanism of PPI in CRPC cell ferroptosis.MethodsProtein levels of GPX4, p‐extracellular regulated protein kinases (ERK), ERK, DNMT1, and ACSL4 were measured by Western blot. DNMT1 and ACSL4 mRNA expression was analyzed by reverse transcription‐quantitative polymerase chain reaction (RT‐qPCR). Prostate cancer cells (DU145, PC3) were treated with PPI. Cell viability was assessed utilizing Cell Counting Kit‐8 (CCK‐8) assay. The role of PPI in regulating ferroptosis was determined by analyzing lipid reactive oxygen species (ROS), malonyl dialdehyde (MDA), iron (Fe2+), and glutathione (GSH) content. Chromatin immunoprecipitation (ChIP) assay verified the effect of DNMT1 on the ACSL4 promoter. The methylation level of ACSL4 promoter was assessed utilizing MSP. A nude mice xenograft was adopted to detect the effect of PPI in vivo.ResultsPPI inhibited CRPC cell proliferation, reduced levels of GSH and GPX4, and increased levels of MDA, Fe2+, and ROS, while ERK inhibitor reversed the effect of PPI on ferroptosis. PPI repressed the methylation level of ACSL4 promoter by inhibiting DNMT1. DNMT1 knockdown promoted CRPC cell ferroptosis by regulating ACSL4. PPI induced ferroptosis and suppressed CRPC growth in nude mice.ConclusionPPI can be used as a ferroptosis inducer to induce ferroptosis in CRPC cells via the ERK/DNMT1/ACSL4 axis, suggesting that PPI may be a new strategy for CRPC treatment.

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ACSL3 and ACSL4, Distinct Roles in Ferroptosis and Cancers

Cited by 79 publications

References 82 publications

Bioinorganic Modulators of Ferroptosis: A Review of Recent Findings

Bioinorganic Modulators of Ferroptosis: A Review of Recent Findings

Targeting ferroptosis in gastric cancer: Strategies and opportunities

Polyphyllin I induces ferroptosis in castration‐resistant prostate cancer cells through the ERK/DNMT1/ACSL4 axis

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