The iron chelator desferrioxamine synergizes with chemotherapy for cancer treatment

Wang, Lingjuan; Li, Xiaoqing; Mu, Yanxi; Lu, Chang; Tang, Shiqian; Lü, Kun; Qiu, Xiaoming; Wei, Aili; Cheng, Yongjiu; Wei, Wei

doi:10.1016/j.jtemb.2019.07.008

Cited by 32 publications

(34 citation statements)

References 35 publications

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“…DFOB, thanks to its clinical safety and documented efficacy in chelation therapy, was the first explored molecule in this context and its administration as supportive anticancer therapy has been tested. It appeared to interfere with DNA synthesis and to inhibit the progression of skin cancer, breast adenocarcinoma, hepatocellular carcinoma and ovarian cancer [ 63 , 64 , 65 , 66 , 67 ]. However, the promising anticancer activity of DFOB is still limited and further studies are required to elucidate its potential benefit as adjuvant therapy in the treatment of malignant tumors.…”

Section: Dfob In Medicinal Chemistry and Other Applicationsmentioning

confidence: 99%

Deferoxamine B: A Natural, Excellent and Versatile Metal Chelator

Bellotti

Remelli

2021

Molecules

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Deferoxamine B is an outstanding molecule which has been widely studied in the past decade for its ability to bind iron and many other metal ions. The versatility of this metal chelator makes it suitable for a number of medicinal and analytical applications, from the well-known iron chelation therapy to the most recent use in sensor devices. The three bidentate hydroxamic functional groups of deferoxamine B are the centerpiece of its metal binding ability, which allows the formation of stable complexes with many transition, lanthanoid and actinoid metal ions. In addition to the ferric ion, in fact, more than 20 different metal complexes of deferoxamine b have been characterized in terms of their chemical speciation in solution. In addition, the availability of a terminal amino group, most often not involved in complexation, opens the way to deferoxamine B modification and functionalization. This review aims to collect and summarize the available data concerning the complex-formation equilibria in solutions of deferoxamine B with different metal ions. A general overview of the progress of its applications over the past decade is also discussed, including the treatment of iron overload-associated diseases, its clinical use against cancer and neurodegenerative disorders and its role as a diagnostic tool.

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Section: Dfob In Medicinal Chemistry and Other Applicationsmentioning

confidence: 99%

Deferoxamine B: A Natural, Excellent and Versatile Metal Chelator

Bellotti

Remelli

2021

Molecules

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“…44,45 A previous study reported that cancer cells with acquired resistance to cisplatin exhibited substantial alterations in the intracellular trace elements content and in the levels of regulatory proteins involved in the cellular uptake, storage and efflux of these elements. 46 Hence, modulating trace elements in the diet 44 or adding metal chelators to synergize with chemotherapy for cancer treatments 47 may promote the activity, reduce the toxicity of antitumor drugs,and even improve the prognosis. 48 On the other hand, determining the variations of trace element level in cells treated with anticancer drugs will be helpful to better understand the mechanism of action, and to guide and improve their clinical applications.…”

Section: Resultsmentioning

confidence: 99%

The Disturbance of Anticancer Drug Cisplatin to Cellular Homeostasis of Trace Elements Revealed by ICP-MS and ToF-SIMS

Jia¹,

Li²,

Zhang³

et al. 2021

At.Spectrosc.

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Trace elements play important roles in many physiological processes. The disorder in the metabolism and/or homeostasis of the trace elements will cause pathogenic changes, and finally lead to the development of diseases. This present work aimed to investigate the effect of anticancer metallodrug cisplatin on the homeostasis of trace metal elements, iron (Fe), zinc (Zn) and copper (Cu), in both human HEK293 normal cells and A549 lung cancer cells by using inductively coupled plasma mass spectrometry (ICP-MS) and time-of-flight secondary ion mass spectrometry (ToF-SIMS). The levels of trace metal elements in both whole cells and nuclei subjected to cisplatin treatment were measured by ICP-MS, and results showed that accompanying with the increasing concentration of cisplatin, the content of Fe inside whole cells and nuclei of both normal and cancer cells increased, implying that cisplatin may induce ferroptosis, contributing to its anticancer activity. While the level of Cu and Zn in the whole cells increased with increase in cisplatin concentration, the level of Cu and Zn, in particular the latter, in nuclei decreased with increase of cisplatin concentration. These implicate that cisplatin may compete with Zn for binding to metalloproteins in nuclei, leading to efflux of Zn from nucleus. The normalized signal intensity of Fe, Zn, and Cu in single cells detected by ToF-SIMS increased accompanying with increased cisplatin concentration, being in line with that obtained by quantitative ICP-MS on large quantity of cells. These findings provide novel insights into better understanding in the mechanism of action of cisplatin.Trace metal elements, such as iron, zinc, copper, are essential in the human body as they consist of many metalloproteins or enzymes which are involved in vital physiological regulation processes and play crucial roles in maintaining the normal function

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“…Chelators are frequently used in combination with other therapies. As an example, DFO was associated with many different chemotherapeutic drugs such as cyclophosphamide, thiotepa, etoposide, carboplatin and cisplatin [121][122][123]. However, some cancers are resistant to Fe-chelators, probably because of their low membrane permeability properties [119].…”

Section: Fe Chelatorsmentioning

confidence: 99%

Iron Dysregulation in Human Cancer: Altered Metabolism, Biomarkers for Diagnosis, Prognosis, Monitoring and Rationale for Therapy

Lelièvre

Sancey

Coll

et al. 2020

Preprint

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Iron (Fe) is a trace element that plays essential roles in various biological processes such as DNA synthesis and repair, as well as cellular energy production, or oxygen transport, and it is currently widely recognized that iron homeostasis is dysregulated in many cancers. Indeed, several iron homeostasis proteins may be responsible for malignant tumor initiation, proliferation, and for metastatic spread of tumors. A large number of studies demonstrated the potential clinical value of turning these deregulated proteins as prognostic and/or predictive biomarkers of malignancy and /or response to anticancer treatments. Additionally, the iron addiction of cancer cells and the importance of iron in ferroptosis cell death signaling pathways prompted the development of therapeutic strategies against advanced stage or resistant cancers. In this review, we selected relevant and promising studies in the field of iron metabolism in cancer research and clinical oncology. Besides, we discuss some co-existing discrepant findings. We will also present and discuss the latest lines of research related to targeting iron, or its regulatory pathways, as potential promising anti-cancer strategies for human therapy. Iron chelators, such as deferoxamine or iron-oxide based nanoparticles, which are already tested in clinical trials, alone or in combination with chemotherapy will also be reported.

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The iron chelator desferrioxamine synergizes with chemotherapy for cancer treatment

Cited by 32 publications

References 35 publications

Deferoxamine B: A Natural, Excellent and Versatile Metal Chelator

Deferoxamine B: A Natural, Excellent and Versatile Metal Chelator

The Disturbance of Anticancer Drug Cisplatin to Cellular Homeostasis of Trace Elements Revealed by ICP-MS and ToF-SIMS

Iron Dysregulation in Human Cancer: Altered Metabolism, Biomarkers for Diagnosis, Prognosis, Monitoring and Rationale for Therapy

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