Crosstalk between ferroptosis and stress—Implications in cancer therapeutic responses

Zhang, Cheng; Yu, Jiaojiao; Yang, Chen; Shang, Shuang; Lv, Xin; Cui, Bing; Hua, Fang

doi:10.1002/cai2.7

Cited by 8 publications

(4 citation statements)

References 161 publications

(209 reference statements)

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“…In recent years, ferroptosis has garnered significant attention from researchers due to its potential implications in drug resistance mechanisms observed across various tumors [27][28][29]. As is widely recognized, the Xc-GSH-GPX4 system represents one of the most crucial cellular antioxidant defense mechanisms against ferroptosis [30].…”

Section: Zhang Et Al Have Demonstrated That Abx Represented Thementioning

confidence: 99%

Albumin-bound paclitaxel augment temozolomide treatment sensitivity of glioblastoma cells by disrupting DNA damage repair and promoting ferroptosis

Qu,

Qi,

Zhang

et al. 2023

J Exp Clin Cancer Res

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Background Temozolomide (TMZ) treatment efficacy in glioblastoma (GBM) patients has been limited by resistance in the clinic. Currently, there are no clinically proven therapeutic options available to restore TMZ treatment sensitivity. Here, we investigated the potential of albumin-bound paclitaxel (ABX), a novel microtubule targeting agent, in sensitizing GBM cells to TMZ and elucidated its underlying molecular mechanism. Methods A series of in vivo and in vitro experiments based on two GBM cell lines and two primary GBM cells were designed to evaluate the efficacy of ABX in sensitizing GBM cells to TMZ. Further proteomic analysis and validation experiments were performed to explore the underlying molecular mechanism. Finally, the efficacy and mechanism were validated in GBM patients derived organoids (PDOs) models. Results ABX exhibited a synergistic inhibitory effect on GBM cells when combined with TMZ in vitro. Combination treatment of TMZ and ABX was highly effective in suppressing GBM progression and significantly prolonged the survival oforthotopic xenograft nude mice, with negligible side effects. Further proteomic analysis and experimental validation demonstrated that the combined treatment of ABX and TMZ can induce sustained DNA damage by disrupting XPC and ERCC1 expression and nuclear localization. Additionally, the combination treatment can enhance ferroptosis through regulating HOXM1 and GPX4 expression. Preclinical drug-sensitivity testing based on GBM PDOs models confirmed that combination therapy was significantly more effective than conventional TMZ monotherapy. Conclusion Our findings suggest that ABX has the potential to enhance TMZ treatment sensitivity in GBM, which provides a promising therapeutic strategy for GBM patients.

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Section: Zhang Et Al Have Demonstrated That Abx Represented Thementioning

confidence: 99%

Albumin-bound paclitaxel augment temozolomide treatment sensitivity of glioblastoma cells by disrupting DNA damage repair and promoting ferroptosis

Qu,

Qi,

Zhang

et al. 2023

J Exp Clin Cancer Res

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“…The genetic approach to regulatory frameworks of p53 involves cellular susceptibility to ferroptosis. By enhancing the susceptibility of bone cells to ferroptosis, p53 inhibits cancer and the accumulation of mutations associated with osteosarcoma ( Zhang et al, 2022a ). Genetic mutations are at the center of p53-induced ferroptosis as genetic mutations affect the expression of cells, protein interactions, and the resulting outcomes.…”

Section: Resultsmentioning

confidence: 99%

The regulatory effects of p53 on the typical and atypical ferroptosis in the pathogenesis of osteosarcoma: A systematic review

Wang

2023

Front. Genet.

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Study background: As a rare condition, osteosarcoma affects approximately 3% of all cancer patients. Its exact pathogenesis remains largely unclear. The role of p53 in up- and down-regulating atypical and typical ferroptosis in osteosarcoma remains unclear. The primary objective of the present study is investigating the role of p53 in regulating typical and atypical ferroptosis in osteosarcoma.Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) and the Patient, Intervention, Comparison, Outcome, and Studies (PICOS) protocol were used in the initial search. The literature search was performed in six electronic databases, including EMBASE, Cochrane library of trials, Web of Science, PubMed, Google Scholar, and Scopus Review, using keywords connected by Boolean operators. We focused on studies that adequately defined patient profiles described by PICOS.Results and discussion: We found that p53 played fundamental up- and down-regulatory roles in typical and atypical ferroptosis, resulting in either advancement or suppression of tumorigenesis, respectively. Direct and indirect activation or inactivation of p53 downregulated its regulatory roles in ferroptosis in osteosarcoma. Enhanced tumorigenesis was attributed to the expression of genes associated with osteosarcoma development. Modulation of target genes and protein interactions, especially SLC7A11, resulted in enhanced tumorigenesis.Conclusion: Typical and atypical ferroptosis in osteosarcoma were regulatory functions of p53. The activation of MDM2 inactivated p53, leading to the downregulation of atypical ferroptosis, whereas activation of p53 upregulated typical ferroptosis. Further studies should be performed on the regulatory roles of p53 to unmask its possible clinical applications in the management of osteosarcoma.

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“…ACSL3 integrates exogenous monounsaturated fatty acids into phospholipids, thereby reducing PUFA incorporation into phospholipids, displacing them from cell membranes, preventing lipid accumulation, and inhibiting ferroptosis. Exogenous monounsaturated fatty acids protect cells against apoptotic lipotoxicity caused by ACSL3-independent saturated FA accumulation [86]. Monounsaturated FAs are not substrates for the lipid peroxidation that occurs during ferroptosis [76].…”

Section: Effects Of Omega-3 Pufa Supplementation On Ferroptosismentioning

confidence: 99%

Can Iron and Polyunsaturated Fatty Acid Supplementation Induce Ferroptosis?

2023

Cell Physiol Biochem

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Ferroptosis is a regulated non-apoptotic cell death process triggered by excessive iron-induced lipid peroxidation. Excess intracellular iron promotes lipid peroxidation by increasing reactive oxygen species formation through the Fenton reaction. Thus, iron and polyunsaturated fatty acid intake may trigger ferroptosis under certain conditions. The aims of this review were to compile and examine evidence in the literature for the effects of iron and polyunsaturated fatty acid supplementation on ferroptosis. Omega-6 polyunsaturated fatty acids have relatively greater susceptibility to lipid peroxidation and could, therefore, participate in ferroptosis. By contrast, omega-3 polyunsaturated fatty acids promote intracellular antioxidants synthesis and reduce the formation of hydroperoxides that induce ferroptosis. As intestinal iron absorption is regulated by iron nutritional status, individuals with normal functioning of the hepcidin-ferroportin axis are at low risk of developing iron overload in response to ingestion of iron-rich foods. Therefore, iron supplementation is potentially toxic mainly for the intestinal epithelium and the microbiota. In animal models, iron-rich diets increased oxidative damage, lowered the glutathione concentration within hepatocytes, and downregulated desaturases that synthesize long-chain polyunsaturated fatty acids. These adverse effects of iron supplementation were prevented by omega-3 fatty acid co-supplementation. The impact of food and supplement intake on ferroptosis has seldom been investigated. Scientific evidence still does not allow us to know for sure whether iron and PUFA supplementation are capable of inducing ferroptosis. As the mechanisms that control ferroptosis can determine whether cells proliferate or die, future studies should directly investigate the effects of nutrient supplementation and food intake on the ferroptosis process in different types of cells and tissues.

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Crosstalk between ferroptosis and stress—Implications in cancer therapeutic responses

Cited by 8 publications

References 161 publications

Albumin-bound paclitaxel augment temozolomide treatment sensitivity of glioblastoma cells by disrupting DNA damage repair and promoting ferroptosis

Albumin-bound paclitaxel augment temozolomide treatment sensitivity of glioblastoma cells by disrupting DNA damage repair and promoting ferroptosis

The regulatory effects of p53 on the typical and atypical ferroptosis in the pathogenesis of osteosarcoma: A systematic review

Can Iron and Polyunsaturated Fatty Acid Supplementation Induce Ferroptosis?

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