The Dual Role of ROS in Hematological Malignancies: Stem Cell Protection and Cancer Cell Metastasis

Samimi, Azin; Khodayar, Mohammad Javad; Alidadi, Hadis; Khodadi, Elahe

doi:10.1007/s12015-019-09949-5

Cited by 32 publications

(19 citation statements)

References 118 publications

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“…e therapeutic agents often represent less toxicity than regular chemotherapeutic drugs, which often kill bulk cancer cells and normal cells, but are impotent for CSC killing. e elevated ROS levels might trigger the differentiation of CSCs including LSCs, and overwhelming concentration of ROS mainly produced from mitochondria may be an optimal treatment to eradicate this cell population during cancer therapy [54,55].…”

Section: Discussionmentioning

confidence: 99%

A Novel Fluorescent Dye Invades Mitochondria to Selectively Kill Cancer Stem Cells via Increased ROS Production

Zhang

Liu

Bai

et al. 2021

Bioinorganic Chemistry and Applications

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Development of multiple agents has a significant impact on the cancer diagnosis and therapy. Several fluorescent dyes including near-infrared (NIR) fluorescent agents have been already well studied in the field of photodynamic therapy (PDT). In the present study, we reported a novel fluorescent dye could obviously inhibit cancer cell proliferation with slight toxic effects on the biological organism. Furthermore, it displayed selective staining on cancer cells, particularly on cancer stem cells (CSCs), rather than normal cells. Mechanically, this dye preferred to invading mitochondria of cancer cells and inducing overwhelming reactive oxygen species (ROS) production. The in vivo experiments further demonstrated that this dye could image cancer cells and even CSCs in a short-time intratumor injection manner using a zebrafish model and subsequently inhibit cancer cell proliferation after a relatively long-time drug exposure. Taken together, the future development of this agent will promise to make an essential contribution to the cancer diagnosis and therapeutics.

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Section: Discussionmentioning

confidence: 99%

A Novel Fluorescent Dye Invades Mitochondria to Selectively Kill Cancer Stem Cells via Increased ROS Production

Zhang

Liu

Bai

et al. 2021

Bioinorganic Chemistry and Applications

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“…Laaper and Jahani-Asl, 2018; Khacho et al, 2019;Samimi et al, 2020). Therefore, fusion impairment may affect proper mitochondria maturation, OXPHOS density and then the production of ROS and ATP.…”

Section: Discussionmentioning

confidence: 99%

Erythroid Differentiation and Heme Biosynthesis Are Dependent on a Shift in the Balance of Mitochondrial Fusion and Fission Dynamics

González-Ibáñez

Ruíz

Jensen

et al. 2020

Front. Cell Dev. Biol.

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Erythropoiesis is the most robust cellular differentiation and proliferation system, with a production of ∼2 × 1011 cells per day. In this fine-tuned process, the hematopoietic stem cells (HSCs) generate erythroid progenitors, which proliferate and mature into erythrocytes. During erythropoiesis, mitochondria are reprogrammed to drive the differentiation process before finally being eliminated by mitophagy. In erythropoiesis, mitochondrial dynamics (MtDy) are expected to be a key regulatory point that has not been described previously. We described that a specific MtDy pattern occurs in human erythropoiesis from EPO-induced human CD34+ cells, characterized predominantly by mitochondrial fusion at early stages followed by fission at late stages. The fusion protein MFN1 and the fission protein FIS1 are shown to play a key role in the progression of erythropoiesis. Fragmentation of the mitochondrial web by the overexpression of FIS1 (gain of fission) resulted in both the inhibition of hemoglobin biosynthesis and the arrest of erythroid differentiation, keeping cells in immature differentiation stages. These cells showed specific mitochondrial features as compared with control cells, such as an increase in round and large mitochondrial morphology, low mitochondrial membrane potential, a drop in the expression of the respiratory complexes II and IV and increased ROS. Interestingly, treatment with the mitochondrial permeability transition pore (mPTP) inhibitor, cyclosporin A, rescued mitochondrial morphology, hemoglobin biosynthesis and erythropoiesis. Studies presented in this work reveal MtDy as a hot spot in the control of erythroid differentiation, which might signal downstream for metabolic reprogramming through regulation of the mPTP.

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“…In addition to the fact that ROS is deeply entangled with hematopoiesis, as a certain amount of ROS is critical for the coordinated proliferation and differentiation of hematopoietic stem cells, excessive ROS levels at first lead to higher stem cell turn-over and ultimately to stem cell exhaustion [ 51 , 52 , 53 ]. Accordingly, in vitro experiments performed with hematopoietic stem cells (HSC) from human bone marrow and in vivo studies in MDS mouse models revealed that HSC, which are exposed to increased ROS levels, have a reduced life span and are earlier exhausted, ultimately leading to lethal impairment of HSC function.…”

Section: Aspects On Iron Ros and Implications For Mdsmentioning

confidence: 99%

EnvIRONmental Aspects in Myelodysplastic Syndrome

Petzer

Theurl

Weiss

et al. 2021

IJMS

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Systemic iron overload is multifactorial in patients suffering from myelodysplastic syndrome (MDS). Disease-immanent ineffective erythropoiesis together with chronic red blood cell transfusion represent the main underlying reasons. However, like the genetic heterogeneity of MDS, iron homeostasis is also diverse in different MDS subtypes and can no longer be generalized. While a certain amount of iron and reactive oxygen species (ROS) are indispensable for proper hematological output, both are harmful if present in excess. Consequently, iron overload has been increasingly recognized as an important player in MDS, which is worth paying attention to. This review focuses on iron- and ROS-mediated effects in the bone marrow niche, their implications for hematopoiesis and their yet unclear involvement in clonal evolution. Moreover, we provide recent insights into hepcidin regulation in MDS and its interaction between erythropoiesis and inflammation. Based on Tet methylcytosine dioxygenase 2 (TET2), representing one of the most frequently mutated genes in MDS, leading to disturbances in both iron homeostasis and hematopoiesis, we highlight that different genetic alteration may have different implications and that a comprehensive workup is needed for a complete understanding and development of future therapies.

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The Dual Role of ROS in Hematological Malignancies: Stem Cell Protection and Cancer Cell Metastasis

Cited by 32 publications

References 118 publications

A Novel Fluorescent Dye Invades Mitochondria to Selectively Kill Cancer Stem Cells via Increased ROS Production

A Novel Fluorescent Dye Invades Mitochondria to Selectively Kill Cancer Stem Cells via Increased ROS Production

Erythroid Differentiation and Heme Biosynthesis Are Dependent on a Shift in the Balance of Mitochondrial Fusion and Fission Dynamics

EnvIRONmental Aspects in Myelodysplastic Syndrome

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