Innovative therapies for neuroblastoma: The surprisingly potent role of iron chelation in up-regulating metastasis and tumor suppressors and down-regulating the key oncogene, N-myc

Wijesinghe, Tharushi; Mahendiran, Dharmasivam; Dai, Charles C; Richardson, Des R.

doi:10.1016/j.phrs.2021.105889

Cited by 26 publications

(24 citation statements)

References 178 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As it entered Phase I clinical trials, DpC held promise to become a new addition to certain oncotherapy protocols. Despite DpC exhibiting superior pharmacokinetic properties (e.g., increased half-life and resistance against inactivation by N-demethylation) over its predecessor Dp44mT [ 67 ], clinical trials have reported myalgia in patients treated with DpC [ 68 ]. Nevertheless, iron chelators still show promising results in potentially treating certain types of neuroblastoma, particularly those with upregulated expression of N-MYC.…”

Section: Discussionmentioning

confidence: 99%

Iron-Chelation Treatment by Novel Thiosemicarbazone Targets Major Signaling Pathways in Neuroblastoma

Macsek

Škoda

Krchniaková

et al. 2021

IJMS

View full text Add to dashboard Cite

Despite constant advances in the field of pediatric oncology, the survival rate of high-risk neuroblastoma patients remains poor. The molecular and genetic features of neuroblastoma, such as MYCN amplification and stemness status, have established themselves not only as potent prognostic and predictive factors but also as intriguing targets for personalized therapy. Novel thiosemicarbazones target both total level and activity of a number of proteins involved in some of the most important signaling pathways in neuroblastoma. In this study, we found that di-2-pyridylketone 4-cyclohexyl-4-methyl-3-thiosemicarbazone (DpC) potently decreases N-MYC in MYCN-amplified and c-MYC in MYCN-nonamplified neuroblastoma cell lines. Furthermore, DpC succeeded in downregulating total EGFR and phosphorylation of its most prominent tyrosine residues through the involvement of NDRG1, a positive prognostic marker in neuroblastoma, which was markedly upregulated after thiosemicarbazone treatment. These findings could provide useful knowledge for the treatment of MYC-driven neuroblastomas that are unresponsive to conventional therapies.

show abstract

Section: Discussionmentioning

confidence: 99%

Iron-Chelation Treatment by Novel Thiosemicarbazone Targets Major Signaling Pathways in Neuroblastoma

Macsek

Škoda

Krchniaková

et al. 2021

IJMS

View full text Add to dashboard Cite

show abstract

“…Lipid peroxidation leads to alterations in the packing of lipid bilayers [3,4], which alters permeability and the phase transition temperature [4,5]. Oxidative stress can participate in oncogenesis and provoke tumor growth [6,7], but also can be implemented as part of the design of anti-cancer therapies [8,9]. The generation of ROS, such as superoxide radical (O 2 • − ), peroxyl radical (ROO • ), hydroxyl radical (OH•), and hydrogen peroxide (H 2 O 2 ), can react with fatty acids, resulting in peroxidation [10].…”

Section: Introductionmentioning

confidence: 99%

Ascorbate-and iron-driven redox activity of Dp44mT and Emodin facilitates peroxidation of micelles and bicelles

Selyutina

Kononova

Koshman

et al. 2022

Biochimica et Biophysica Acta (BBA) - General Subjects

View full text Add to dashboard Cite

“…The role of the former in neuroblastoma is unclear. However, iron is increasingly linked to neuroblastoma, because there is an elevated requirement for iron in the disease ( 28 , 29 ), and because there is an emerging link between MYCN and ferroptosis- a type of cell death mediated by iron ( 30 ). However, it is unclear whether GAPDH-mediated iron uptake has any role in ferroptosis in neuroblastoma.…”

Section: Gapdh At the Plasma Membranementioning

confidence: 99%

GAPDH in neuroblastoma: Functions in metabolism and survival

et al. 2022

View full text Add to dashboard Cite

Neuroblastoma is a pediatric cancer of neural crest cells. It develops most frequently in nerve cells around the adrenal gland, although other locations are possible. Neuroblastomas rely on glycolysis as a source of energy and metabolites, and the enzymes that catalyze glycolysis are potential therapeutic targets for neuroblastoma. Furthermore, glycolysis provides a protective function against DNA damage, and there is evidence that glycolysis inhibitors may improve outcomes from other cancer treatments. This mini-review will focus on glyceraldehyde 3-phosphate dehydrogenase (GAPDH), one of the central enzymes in glycolysis. GAPDH has a key role in metabolism, catalyzing the sixth step in glycolysis and generating NADH. GAPDH also has a surprisingly diverse number of localizations, including the nucleus, where it performs multiple functions, and the plasma membrane. One membrane-associated function of GAPDH is stimulating glucose uptake, consistent with a role for GAPDH in energy and metabolite production. The plasma membrane localization of GAPDH and its role in glucose uptake have been verified in neuroblastoma. Membrane-associated GAPDH also participates in iron uptake, although this has not been tested in neuroblastoma. Finally, GAPDH activates autophagy through a nuclear complex with Sirtuin. This review will discuss these activities and their potential role in cancer metabolism, treatment and drug resistance.

show abstract

Innovative therapies for neuroblastoma: The surprisingly potent role of iron chelation in up-regulating metastasis and tumor suppressors and down-regulating the key oncogene, N-myc

Cited by 26 publications

References 178 publications

Iron-Chelation Treatment by Novel Thiosemicarbazone Targets Major Signaling Pathways in Neuroblastoma

Iron-Chelation Treatment by Novel Thiosemicarbazone Targets Major Signaling Pathways in Neuroblastoma

Ascorbate-and iron-driven redox activity of Dp44mT and Emodin facilitates peroxidation of micelles and bicelles

GAPDH in neuroblastoma: Functions in metabolism and survival

Contact Info

Product

Resources

About