Ferroptosis in hematological malignancies and its potential network with abnormal tumor metabolism

Zhang, Jiasi; Liu, Yuxi; Li, Qun; Xu, Aihua; Hu, Yu; Sun, Chaoyang

doi:10.1016/j.biopha.2022.112747

Cited by 27 publications

(22 citation statements)

References 188 publications

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“…The mechanistic studies demonstrated that ART derivatives could significantly increase intracellular reactive oxygen species in cancer cells, which result in ferroptosis, a new regulated cell death pathway, and displays characteristics that transparently differ from apoptosis, autophagy, and necroptosis. [12,25] Based on that, ferroptosis was at least one of the mechanisms for the synthesized ART-isatin hybrids, and more experiments are needed to verify.…”

Section: Resultsmentioning

confidence: 99%

Artemisinin‐isatin hybrids tethered via ethylene linker and their anti‐lung cancer activity

Wang

Zhang

Chen

2022

Archiv der Pharmazie

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The synthesized 11 artemisinin-isatin hybrids 5a-c and 6a-h tethered via ethylene linker were assessed for their in vitro antiproliferative activity against A549 and H1299 nonsmall-cell lung cancer cell lines as well as their cytotoxicity towards BEAS-2B human normal lung epithelial cells. The preliminary results showed that hybrids 5a-c and 6a-h did not show any cytotoxicity (IC 50 : >100 µM) on BEAS-2B cells, and also possessed potential activity (IC 50 : 6.99-76.49 µM) against A549 and H1299 lung cancer cell lines. The representative hybrid 6c (IC 50 : 6.99 and 7.57 µM) was far more potent than artemisinin (IC 50 : >100 µM) and dihydroartemisinin (IC 50 : >100 µM), and was slightly less active than doxorubicin (IC 50 : 4.14 and 2.77 µM). Moreover, hybrid 6c also exhibited an excellent safety profile and good selectivity with SI values of >13.21. Therefore, hybrid 6c could serve as a promising candidate for further in vivo evaluations.

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Section: Resultsmentioning

confidence: 99%

Artemisinin‐isatin hybrids tethered via ethylene linker and their anti‐lung cancer activity

Wang

Zhang

Chen

2022

Archiv der Pharmazie

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“…Ferroptosis, a newly defined type of programmed cell death, is closely related to oxidative stress and the disruption of redox homeostasis is also crucial for the chemoresistance of tumour cells ( 159 ). Wu et al ( 160 ) indicated that nanodrugs with silica particles used as carriers are able to dissolve and release Fe 3 O 4 particles and glutaminase inhibitors under acidic conditions, thus consuming glutathione in tumour cells and reversing the drug resistance of tumour cells to oxaliplatin by inducing ROS-dependent ferroptosis.…”

Section: Future Perspectivesmentioning

confidence: 99%

NcRNAs: Multi‑angle participation in the regulation of glioma chemotherapy resistance (Review)

et al. 2022

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As the most common primary tumour of the central nervous system, gliomas have a high recurrence rate after surgical resection and are resistant to chemotherapy, particularly high-grade gliomas dominated by glioblastoma multiforme (GBM). The prognosis of GBM remains poor despite improvements in treatment modalities, posing a serious threat to human health. At present, although drugs such as temozolomide, cisplatin and bevacizumab, are effective in improving the overall survival of patients with GBM, most patients eventually develop drug resistance, leading to poor clinical prognosis. The development of multidrug resistance has therefore become a major obstacle to improving the effectiveness of chemotherapy for GBM. The ability to fully understand the underlying mechanisms of chemotherapy resistance and to develop novel therapeutic targets to overcome resistance is critical to improving the prognosis of patients with GBM. Of note, growing evidence indicates that a large number of abnormally expressed noncoding RNAs (ncRNAs) have a central role in glioma chemoresistance and may target various mechanisms to modulate chemosensitivity. In the present review, the roles and molecular mechanisms of ncRNAs in glioma drug resistance were systematically summarized, the potential of ncRNAs as drug resistance markers and novel therapeutic targets of glioma were discussed and prospects for glioma treatment were outlined. ncRNAs are a research direction for tumor drug resistance mechanisms and targeted therapies, which not only provides novel perspectives for reversing glioma drug resistance but may also promote the development of precision medicine for clinical diagnosis and treatment.

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“…Numerous studies have implicated ferroptosis as critical for the eradication of carcinogenic cells and suppression of cancer growth [7][8][9][10]. The importance of ferroptosis in hematological malignancies has been investigated in an increasing number of studies [11][12][13][14].…”

Section: Introductionmentioning

confidence: 99%

Dual inhibition of thioredoxin 1/ glutathione induces ferroptosis in chronic myeloid leukemia cells

Cao

Sun

Zhang

et al. 2023

Preprint

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Ferroptosis is an iron-dependent cell death induced by the oxidation of polyunsaturated fatty acids. In recent years, ferroptosis has garnered tremendous potential in cancer therapy. However, the significance pathways of ferroptosis in chronic myeloid leukemia (CML) therapy are still poorly understood. Here, we investigated the role of a critical antioxidant protein, thioredoxin 1 (Trx1), in regulating ferroptosis in CML cells. First, we showed that Trx1 expression was higher in patients with CML than in healthy controls. Specifically, Trx1 knockdown suppressed cell growth and slowed tumor progression in xenograft models. Pharmacological inhibitors of Trx1 also attenuated cell growth, reduced colony formation, and caused CML cell death. Second, we showed that decreased Trx1 expression enhanced the cytotoxicity of the glutathione (GSH) biosynthesis inhibitor buthionine sulfoximine. Mechanistically, the combined inhibition of Trx1 and GSH synthesis disrupted the homeostasis of cellular reactive oxygen species as evidenced by increased ROS and malondialdehyde; and decreased GSH. Importantly, inhibition of Trx1 significantly resentisized GSH-depletion induced ferroptosis in CML cells. Finally, targeting Trx1 and GSH synthesis with small-molecule inhibitors caused a synergic effect on CML cells both in vitro and in vivo.Together, these results highlight an critical role of Trx1 in GSH-depletion induced ferroptosis and provide clues for dual inhibition of the Trx1 and GSH system as a combinatorial strategy for CML therapy.

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Ferroptosis in hematological malignancies and its potential network with abnormal tumor metabolism

Cited by 27 publications

References 188 publications

Artemisinin‐isatin hybrids tethered via ethylene linker and their anti‐lung cancer activity

Artemisinin‐isatin hybrids tethered via ethylene linker and their anti‐lung cancer activity

NcRNAs: Multi‑angle participation in the regulation of glioma chemotherapy resistance (Review)

Dual inhibition of thioredoxin 1/ glutathione induces ferroptosis in chronic myeloid leukemia cells

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