The Chemistry and Biology of Ferroptosis

Stockwell, Brent R.; Jiang, Xuejun

doi:10.1016/j.chembiol.2020.03.013

Cited by 247 publications

(219 citation statements)

References 104 publications

Supporting

Mentioning

214

Contrasting

Unclassified

Order By: Relevance

“…Ferroptosis is recently discovered iron-dependent cell death fueled by lipid peroxidation, which differs from necrosis and apoptosis [ 322 – 324 ]. Mitochondrial metabolism involved series of substrates consumption, is primary source of ROS via Fenton reaction that ferrous iron mixed with hydrogen peroxide (H 2 O 2 ) is equipped with strong oxidizability to oxidize many known intracellular compounds such as carboxylic acids, alcohols and esters into inorganic states with significant oxidation effect [ 325 ].…”

Section: Hypoxia and Targeted Therapy Via Epigenetic Interferencementioning

confidence: 99%

“…Interestingly, it’s reported that hypoxic tumors with HIF-1 over-expression inhibits acyl-CoA dehydrogenases leads to tumor progression via ROS alteration [ 209 ]. Over the past 20 years, small-molecule inhibitors, including system x c -Inhibitors, GPX4 inhibitors, RTAs, CoQ10 pathway inhibitors, endoperoxides, and iron chelators and sources inhibitors etc., have been applied in ferroptosis-associated diseases [ 322 ], and mechanisms behind these inhibition effects may reappear in HIF signaling, which remains under-reported.…”

Section: Hypoxia and Targeted Therapy Via Epigenetic Interferencementioning

confidence: 99%

See 1 more Smart Citation

Epigenetic crosstalk between hypoxia and tumor driven by HIF regulation

Mao

Wang

et al. 2020

J Exp Clin Cancer Res

View full text Add to dashboard Cite

Hypoxia is the major influence factor in physiological and pathological courses which are mainly mediated by hypoxia-inducible factors (HIFs) in response to low oxygen tensions within solid tumors. Under normoxia, HIF signaling pathway is inhibited due to HIF-α subunits degradation. However, in hypoxic conditions, HIF-α is activated and stabilized, and HIF target genes are successively activated, resulting in a series of tumour-specific activities. The activation of HIFs, including HIF-1α, HIF-2α and HIF-3α, subsequently induce downstream target genes which leads to series of responses, the resulting abnormal processes or metabolites in turn affect HIFs stability. Given its functions in tumors progression, HIFs have been regarded as therapeutic targets for improved treatment efficacy. Epigenetics refers to alterations in gene expression that are stable between cell divisions, and sometimes between generations, but do not involve changes in the underlying DNA sequence of the organism. And with the development of research, epigenetic regulation has been found to play an important role in the development of tumors, which providing accumulating basic or clinical evidences for tumor treatments. Here, given how little has been reported about the overall association between hypoxic tumors and epigenetics, we made a more systematic review from epigenetic perspective in hope of helping others better understand hypoxia or HIF pathway, and providing more established and potential therapeutic strategies in tumors to facilitate epigenetic studies of tumors.

show abstract

Section: Hypoxia and Targeted Therapy Via Epigenetic Interferencementioning

confidence: 99%

Section: Hypoxia and Targeted Therapy Via Epigenetic Interferencementioning

confidence: 99%

Epigenetic crosstalk between hypoxia and tumor driven by HIF regulation

Mao

Wang

et al. 2020

J Exp Clin Cancer Res

View full text Add to dashboard Cite

show abstract

“…To determine whether H 2 O 2 -mediated cell death occurs via apoptosis or ferroptosis, the cells were treated with Liperfluo or Annexin V and PI followed by flow cytometry analysis. Liperfluo is a ferroptosis marker [ 31 ] and Annexin V is an apoptosis marker. Our results showed that Liperfluo increased more than Annexin V in both HeLa and SAS ρ 0 cells after 3-h H 2 O 2 treatment (1.55 vs. 1.15-fold in HeLa ρ 0 cells and 3.79 vs 1.63-fold in SAS ρ 0 cells, Fig.…”

Section: Resultsmentioning

confidence: 99%

Mitochondrial dysfunction promotes aquaporin expression that controls hydrogen peroxide permeability and ferroptosis

Takashi

Tomita²,

Kuwahara

et al. 2020

Free Radical Biology and Medicine

View full text Add to dashboard Cite

Most anti-cancer agents and radiotherapy exert their therapeutic effects via the production of free radicals. Ferroptosis is a recently described cell death process that is accompanied by iron-dependent lipid peroxidation. Hydrogen peroxide (H 2 O 2 ) has been reported to induce cell death. However, it remains controversial whether H 2 O 2 -induced cell death is ferroptosis. In the present study, we aimed to elucidate the involvement of mitochondria in H 2 O 2 -induced ferroptosis and examined the molecules that regulate ferroptosis. We found that one mechanism underlying H 2 O 2 -induced cell death is ferroptosis, which occurs soon after H 2 O 2 treatment (within 3 h after H 2 O 2 treatment). We also investigated the involvement of mitochondria in H 2 O 2 -induced ferroptosis using mitochondrial DNA-depleted ρ 0 cells because ρ 0 cells produce more lipid peroxidation, hydroxyl radicals ( • OH), and are more sensitive to H 2 O 2 treatment. We found that ρ 0 cells contain high Fe 2+ levels that lead to • OH production by H 2 O 2 . Further, we observed that aquaporin (AQP) 3, 5, and 8 bind nicotinamide-adenine dinucleotide phosphate oxidase 2 and regulate the permeability of extracellular H 2 O 2 , thereby contributing to ferroptosis. Additionally, the role of mitochondria in ferroptosis was investigated using mitochondrial transfer in ρ 0 cells. When mitochondria were transferred into ρ 0 cells, the cells exhibited no sensitivity to H 2 O 2 -induced cytotoxicity because of decreased Fe 2+ levels. Moreover, mitochondrial transfer upregulated the mitochondrial quality control protein prohibitin 2 (PHB2), which contributes to reduced AQP expression. Our findings also revealed the involvement of AQP and PHB2 in ferroptosis. Our results indicate that H 2 O 2 treatment enhances AQP expression, Fe 2+ level, and lipid peroxidation, and decrease mitochondrial function by downregulating PHB2, and thus, is a promising modality for effective cancer treatment.

show abstract

“…During lipid oxidation, GPX4 is the primary enzyme that prevents ferroptosis (Stockwell et al, 2017;Seibt et al, 2019). Many studies have shown that ROS inhibitors (e.g., ferrostatins-1, liproxstatin-1, vitamin E, vitamin C, and beta-carotene), along with GPX4 and its promoters (e.g., dopamine and selenium), are effective in preventing ferroptosis in animal models (Imai et al, 2017;Stockwell, 2018;Bai et al, 2019;Tang and Tang, 2019;Stockwell and Jiang, 2020). For example, the ROS inhibitors ferrostatin-1 and vitamin C aggravate ROS generation and block lipid peroxidation, and vitamin E may inhibit lipoxygenases (Zilka et al, 2017;Hinman et al, 2018;.…”

Section: Inhibitors Of Lipid Ros Generationmentioning

confidence: 99%