An iron hand over cancer stem cells

Hamaï, Ahmed; Cañeque, Tatiana; Müller, Sebastian; Thi, Trang; Hienzsch, Antje; Ginestier, Christophe; Charafe‐Jauffret, Emmanuelle; Codogno, Patrice; Mehrpour, Maryam; Rodriguez, Raphaël

doi:10.1080/15548627.2017.1327104

Cited by 51 publications

(37 citation statements)

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“…Accordingly, in a very recent paper 56 , it has been reported a pronounced effect of ironomycin, an inducer of ferroptosis, against CSCs derived from breast human mammary epithelial cells. These findings could directly implicate that iron homeostasis could represent a key regulator of the survival or death of CSCs 57 . Accordingly, in GSCs we detected an activation of cathepsin B that may be due to lysosome membrane permeabilization, lipid peroxidation, and decreased endogenous levels of the reduced form of glutathione, which is consistent with the induction of ferroptotic cell death.…”

Section: Discussionmentioning

confidence: 91%

Inhibition of autophagy increases susceptibility of glioblastoma stem cells to temozolomide by igniting ferroptosis

et al. 2018

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The role of autophagy in cancer onset and progression appears still controversial. On one hand, autophagy allows cancer cell to survive in unfavorable environmental conditions, on the other hand, once internal energy resources are exhausted, it leads to cell death. In addition, autophagy interpheres with cell cycle progression, de facto exerting a cytostatic activity. Hence, it represents an important target for anticancer therapy. For example, temozolomide (TMZ), of use for glioblastoma (GBM) treatment, appears as capable of inducing autophagy partially inhibiting cancer cell proliferation. However, GBM, a very aggressive brain tumor with poor prognosis even after surgery and radio-chemotherapy, invariably recurs and leads to patient death. Since cancer stem cells have been hypothesized to play a role in refractory/relapsing cancers, in the present work we investigated if autophagy could represent a constitutive cytoprotection mechanism for glioblastoma stem-like cells (GSCs) and if the modulation of autophagic process could affect GBM growth and survival. Thus, in the present study we first evaluated the relevance of autophagy in GBM tumor specimens, then its occurrence in GSCs and, finally, if modulation of autophagy could influence GSC response to TMZ. Our results suggested that, in vitro, the impairing autophagic process with quinacrine, a compound able to cross the blood-brain barrier, increased GSC susceptibility to TMZ. Death of GSCs was apparently due to the iron dependent form of programmed cell death characterized by the accumulation of lipid peroxides called ferroptosis. These results underscore the relevance of the modulation of autophagy in the GSC survival and death and suggest that triggering of ferroptosis in GSCs could represent a novel and important target for the management of glioblastoma.

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Section: Discussionmentioning

confidence: 91%

Inhibition of autophagy increases susceptibility of glioblastoma stem cells to temozolomide by igniting ferroptosis

et al. 2018

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“…In addition, a new type of programmed cell death, ferroptosis, is also closely related to Fe 2+ and the Fenton reaction[ 177 ]. Some researchers have found that ferricin chelates lysosomal iron[ 178 ]. These compounds induce iron depletion by preventing iron transport, leading to the dissolution of ferritin.…”

Section: Impact Of Ros From Pdt On Cscsmentioning

confidence: 99%

Photodynamic therapy regulates fate of cancer stem cells through reactive oxygen species

Zhang

Wang

et al. 2020

WJSC

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Photodynamic therapy (PDT) is an effective and promising cancer treatment. PDT directly generates reactive oxygen species (ROS) through photochemical reactions. This oxygen-dependent exogenous ROS has anti-cancer stem cell (CSC) effect. In addition, PDT may also increase ROS production by altering metabolism, endoplasmic reticulum stress, or potential of mitochondrial membrane. It is known that the half-life of ROS in PDT is short, with high reactivity and limited diffusion distance. Therefore, the main targeting position of PDT is often the subcellular localization of photosensitizers, which is helpful for us to explain how PDT affects CSC characteristics, including differentiation, self-renewal, apoptosis, autophagy, and immunogenicity. Broadly speaking, excess ROS will damage the redox system and cause oxidative damage to molecules such as DNA, change mitochondrial permeability, activate unfolded protein response, autophagy, and CSC resting state. Therefore, understanding the molecular mechanism by which ROS affect CSCs is beneficial to improve the efficiency of PDT and prevent tumor recurrence and metastasis. In this article, we review the effects of two types of photochemical reactions on PDT, the metabolic processes, and the biological effects of ROS in different subcellular locations on CSCs.

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“…In human H460 and H292 NSCLC cells, the subchronic exposure to ironinduced oxidative stress leads to a remarkable increase in CSC spheroids in parallel with an increase in ABCG2 CSC marker [60]. Accordingly, Hamai, et al demonstrate that iron-depletion, followed by an overproduction of ROS, promotes cancer stem cell death [61]. In SKOV3 epithelial ovarian cancer cells, low FHC levels promote cancer stem cell spheroids accumulation along with the increase in stemness markers expression most likely through an iron-independent mechanism involving the regulation of miR-150 and miR-146a [34].…”

Section: Ferritin and Cancer Stem Cellsmentioning

confidence: 99%

Ferritin Heavy Chain: From Redox Cycling to Cancer Biology

Biamonte¹

2018

IJBP

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Iron is an essential nutrient for physiological cellular functions: as cofactor for key enzymes, it is involved in DNA duplication and repair thus representing a key element for cell replication, metabolism and growth. Due to its main role in iron storage, ferritin has been largely referred as redox-related protein for many years. However, increasing evidences suggest that perturbations of intracellular steady state amount of ferritin, and particularly of its heavy subunit (FHC), are key events in the pathogenesis of cancer initiation and progression. In the past decade many studies have demonstrated that FHC participates in cancer related pathways such as growth suppressor evasion, angiogenesis, epithelial to mesenchymal transition (EMT), dysregulation of chemokine signalling and enhanced stem cell expansion. The molecular mechanisms whereby FHC exerts these activities are either iron-dependent or ironindependent. Among the latters, the ability to regulate critical oncogenes (c-myc, NF-kB) or tumor suppressors (p53) as well as to modulate oncomiRNAs expression and chemokine signalling (CXCR4) strongly suggests that FHC is a much more versatile protein than simply iron storage. The deep understanding of these novel and still not completely characterized functions, as well as the discovery of other potential properties, position ferritin as a promising target in cancer therapy.

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An iron hand over cancer stem cells

Cited by 51 publications

References 0 publications

Inhibition of autophagy increases susceptibility of glioblastoma stem cells to temozolomide by igniting ferroptosis

Inhibition of autophagy increases susceptibility of glioblastoma stem cells to temozolomide by igniting ferroptosis

Photodynamic therapy regulates fate of cancer stem cells through reactive oxygen species

Ferritin Heavy Chain: From Redox Cycling to Cancer Biology

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