Deferoxamine Promotes MDA-MB-231 Cell Migration and Invasion through Increased ROS-Dependent HIF-1a Accumulation

Liu, Yiping; Cui, Yong-Feng; Shi, Miao; Zhang, Qiang; Wang, Qiang; Chen, Xiaodong

doi:10.1159/000358674

Cited by 64 publications

(47 citation statements)

References 39 publications

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“…Although multiple studies reported that accumulation of ROS regulated autophagy by pathways such as: i) oxidization of ATG4 leading to accumulation of autophagosomes; ii) activation of the AMPK signaling cascade inducing the initiation of autophagy through the ULK1 complex; iii) disruption of BECN1-BCL-2 interaction leading to the initiation of autophagy; or iv) alteration of mitochondria homeostasis leading to mitophagy activation (75). Furthermore, reactive oxygen/nitrogen species (ROS/RNS) generated in the context of radiation exposure are essential activators of cytoplasmic signaling cascades such as p38 MAPK, JNK, HIF-1α, which play essential roles in the regulation of autophagy (91).…”

Section: Ros and Autophagymentioning

confidence: 99%

Crosstalk between autophagy and intracellular radiation response (Review)

Wang

Huang

et al. 2016

International Journal of Oncology

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Abstract. Autophagy induced by radiation is critical to cell fate decision. Evidence now sheds light on the importance of autophagy induced by cancer radiotherapy. Traditional view considers radiation can directly or indirectly damage DNA which can activate DNA damage the repair signaling pathway, a large number of proteins participating in DNA damage repair signaling pathway such as p53, ATM, PARP1, FOXO3a, mTOR and SIRT1 involved in autophagy regulation. However, emerging recent evidence suggests radiation can also cause injury to extranuclear targets such as plasma membrane, mitochondria and endoplasmic reticulum (ER) and induce accumulation of ceramide, ROS, and Ca 2+ concentration which activate many signaling pathways to modulate autophagy. Herein we review the role of autophagy in radiation therapy and the potent intracellular autophagic triggers induced by radiation. We aim to provide a more theoretical basis of radiation-induced autophagy, and provide novel targets for developing cytotoxic drugs to increase radiosensitivity. Contents1. Introduction 2. The role of autophagy in radiotherapy 3. DNA damage repair and autophagy 4. Mitochondrial damage and autophagy 5. ER stress and autophagy 6. ROS and autophagy 7. Ceramide and autophagy 8. Ca 2+ and autophagy 9. Targeting autophagy for radiotherapy 10. Conclusion IntroductionRadiotherapy is an effective strategy for the treatment of many kinds of cancer to kill or control the malignant tumor cells. However, its benefits have been limited due to radiation resistance. It is imperative to identify new targets and develop cytotoxic drugs to increase radiosensitivity. Radiosensitization has traditionally been performed with agents known to induce apoptosis. However, recent studies demonstrate autophagy induced by radiation also plays an important role in cancer Crosstalk between autophagy and intracellular radiation response (Review)

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Section: Ros and Autophagymentioning

confidence: 99%

Crosstalk between autophagy and intracellular radiation response (Review)

Wang

Huang

et al. 2016

International Journal of Oncology

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“…As shown in a previous study, DFO induces hypoxia and the consequent expression of hypoxiainducible factor-1 alpha (HIF-1α) in breast cancer cells [15]. HIF-1α initiates the transcription of genes encoding angiogenesis-promoting proteins such as vascular endothelial growth factor [16].…”

Section: Discussionmentioning

confidence: 99%

Inhibitory effects of iron depletion plus eribulin on the breast cancer microenvironment

Goto

Kashiwagi

Asano

et al. 2020

Preprint

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Background Iron is required for the proliferation of cancer cells, and its depletion suppresses tumor growth. Eribulin mesylate (eribulin), a non-taxane microtubule inhibitor, disrupts the tumor microenvironment via vascular remodeling and obstruction of the epithelial-mesenchymal transition (EMT). Herein, we investigated the effects of the iron chelator deferoxamine (DFO) on tumor-related properties of breast cancer cells and the effects of DFO plus eribulin on tumor growth in vivo . MethodsA triple-negative breast cancer (TNBC) cell line (MDA-MB-231) was used in our study. Cell proliferation, cell migration, cell cycle position, and gene expression were analyzed via MTT assays, wound-healing assays, flow cytometry, and quantitative real-time-polymerase chain reaction, respectively. For the in vivo experiments, mice with MDA-MB-231 xenografts were treated with the inhibitors, alone or together, and tumor volume was determined. Results DFO inhibited breast cancer cell proliferation and migration and decreased the proportion of S-phase cells. Conversely, it induced hypoxia, angiogenesis, EMT, and immune checkpoints, as determined by quantifying the expression of marker mRNAs. Eribulin suppressed the expression of the EMT marker mRNAs in the presence of DFO. DFO plus eribulin inhibited tumor growth in vivo to a greater extent than did either inhibitor alone. Conclusions Although DFO induces oncogenic events (hypoxia, angiogenesis, EMT, and immune checkpoints), it may be an effective treatment for breast cancer when administered in combination with eribulin.

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“…Elevated subunit HIF-1α in the cellular nucleus and cytoplasm further regulates the expression of several target genes that are engaged in neuroprotection, erythropoiesis, and apoptosis modulation in protecting tissues against hypoxic conditions [14][15][16][17]. Furthermore, inadequate oxygen supply likely appears in the brain regions while ICH occurs and abnormalities of HIF-1α are also observed in diabetes.…”

Section: Introductionmentioning

confidence: 99%

Role for HIF-1α and Downstream Pathways in Regulating Neuronal Injury after Intracerebral Hemorrhage in Diabetes

Tang

Chen

et al. 2015

Cell Physiol Biochem

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This is an Open Access article licensed under the terms of the Creative Commons AttributionNonCommercial 3.0 Unported license (CC BY-NC) (www.karger.com/OA-license), applicable to the online version of the article only. Distribution permitted for non-commercial purposes only.Copyright © 2015 S. Karger AG, Basel Key Words Intracerebral hemorrhage • HIF-1α • VEGF • DiabetesAbstract Background/Aims: HIF-1α is accumulated in the cellular nucleus and cytoplasm under conditions of oxygen deprivation and engaged in pathophysiologic changes of homeostasis by modulating the expression of several target genes. As an endogenous signaling protein, HIF-1α contributes to in neuroprotection, erythropoiesis, and apoptosis modulation. The purpose of this study was to examine the role played by HIF-1α in regulating neurological injury evoked by intracerebral hemorrhage (ICH) through its downstream product, namely vascular endothelial growth factor (VEGF). In particular, we examined the effects of diabetic hyperglycemia on HIF-1α response in the processing of ICH. Methods: ELISA was used to measure HIF-1α and VEGF; and Western Blot analysis to examine the protein expression of VEGFR-2 and Caspase-3. Neurological Severity Score and brain water content were used to indicate neurological function and brain edema. Results: HIF-1α and VEGF were significantly increased in the brain after induction of ICH in non-diabetic control rats and diabetic rats; however, the amplified levels of HIF-1α and VEGF were attenuated in diabetic rats (P<0.05 vs. non-diabetic rats) as compared with non-diabetic rats. Also, the protein expression of VEGF receptor subtype 2 was significantly less in the brain of diabetic rats (P<0.05 vs. nondiabetic rats). Further, cerebral infusion of HIF-1 activator stabilized VEGF levels, attenuated Caspase-3 and improved neurological deficits induced by ICH and the effects are smaller in diabetic animals. Conclusion: HIF-1α activated by ICH likely plays a beneficial role via VEGF mechanisms and response of HIF-1α is largely impaired in diabetes. This has pharmacological implications to target specific HIF-1α and VEGF pathway for neuronal dysfunction and vulnerability related to ICH.

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Deferoxamine Promotes MDA-MB-231 Cell Migration and Invasion through Increased ROS-Dependent HIF-1a Accumulation

Cited by 64 publications

References 39 publications

Crosstalk between autophagy and intracellular radiation response (Review)

Crosstalk between autophagy and intracellular radiation response (Review)

Inhibitory effects of iron depletion plus eribulin on the breast cancer microenvironment

Role for HIF-1α and Downstream Pathways in Regulating Neuronal Injury after Intracerebral Hemorrhage in Diabetes

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