A novel inhibitor of tumorspheres reveals the activation of the serine biosynthetic pathway upon mitochondrial inhibition

Subedi, Amit; Muroi, Makoto; Futamura, Yushi; Kawamura, Tatsuro; Aono, Harumi; Nishi, Mayuko; Ryo, Akihide; Watanabe, Nobumoto; Osada, Hiroyuki

doi:10.1002/1873-3468.13361

Cited by 5 publications

(2 citation statements)

References 40 publications

(65 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It has been established that mitochondrial dysfunction causes changes in one-carbon metabolism and that cancer cells will depend even more on their serine/glycine synthesis upon mitochondrial inhibition (33,34). Furthermore, serine/glycine synthesis and the tricarboxylic acid (TCA) cycle are strongly interconnected, implying that targeting both pathways might further metabolically disrupt cancer cells.…”

Section: Sertraline Has Clinical Potential Especially When Used In Combination Therapymentioning

confidence: 99%

Repurposing the Antidepressant Sertraline as SHMT Inhibitor to Suppress Serine/Glycine Synthesis–Addicted Breast Tumor Growth

Geeraerts

Kampen

Rinaldi

et al. 2021

Molecular Cancer Therapeutics

View full text Add to dashboard Cite

SLG received a SB PhD fellowship from "Fonds Wetenschappelijk Onderzoek (FWO) (1S14517N). KRK was supported by a PDM postdoctoral mandate fellowship obtained from the KU Leuven, the "Emmanuel van der Schueren" postdoctoral fellowship from "Kom op tegen Kanker" and a research grant from FWO (FWO KAN2018 1501419N). GR is supported by consecutive PhD fellowships from the "Emmanuel van der Schueren -Kom op tegen Kanker" foundation and FWO (1137117N and 1137119N). PG and AV acknowledge a research grant from FWO (G0F9316N Odysseus). SV

show abstract

Section: Sertraline Has Clinical Potential Especially When Used In Combination Therapymentioning

confidence: 99%

Repurposing the Antidepressant Sertraline as SHMT Inhibitor to Suppress Serine/Glycine Synthesis–Addicted Breast Tumor Growth

Geeraerts

Kampen

Rinaldi

et al. 2021

Molecular Cancer Therapeutics

View full text Add to dashboard Cite

show abstract

“…Serine transmethylation product (catalyzed by serine hydroxymethyltransferase; SHMT, EC 2.1.2.1), glycine, was decreased in crGART, crPFAS, and crADSL cells. Subedi et al reported higher basal levels of SSP enzymes in HeLa cells [ 51 ]. A study of the NCI60 panel showed that glycine conversion increases the rate of proliferation and significantly supplies PDNS [ 42 ], which were both metabolic processes greatly affected in our study given the cellular model and experimental conditions.…”

Section: Discussionmentioning

confidence: 99%

Combined Targeted and Untargeted Profiling of HeLa Cells Deficient in Purine De Novo Synthesis

et al. 2022

View full text Add to dashboard Cite

Three genetically determined enzyme defects of purine de novo synthesis (PDNS) have been identified so far in humans: adenylosuccinate lyase (ADSL) deficiency, 5-amino-4-imidazole carboxamide-ribosiduria (AICA-ribosiduria), and deficiency in bifunctional enzyme phosphoribosylaminoimidazole carboxylase and phosphoribosylaminoimidazolesuccinocarboxamide synthase (PAICS). Clinical signs of these defects are mainly neurological, such as seizures, psychomotor retardation, epilepsy, autistic features, etc. This work aims to describe the metabolic changes of CRISPR-Cas9 genome-edited HeLa cells deficient in the individual steps of PDNS to better understand known and potential defects of the pathway in humans. High-performance liquid chromatography coupled with mass spectrometry was used for both targeted and untargeted metabolomic analyses. The statistically significant features from the untargeted study were identified by fragmentation analysis. Data from the targeted analysis were processed in Cytoscape software to visualize the most affected metabolic pathways. Statistical significance of PDNS intermediates preceding deficient enzymes was the highest (p-values 10 × 10−7–10 × 10−15) in comparison with the metabolites from other pathways (p-values of up to 10 × 10−7). Disturbed PDNS resulted in an altered pool of adenine and guanine nucleotides. However, the adenylate energy charge was not different from controls. Different profiles of acylcarnitines observed among deficient cell lines might be associated with a specific enzyme deficiency rather than global changes related to the PDNS pathway. Changes detected in one-carbon metabolism might reduce the methylation activity of the deficient cells, thus affecting the modification state of DNA, RNA, and proteins.

show abstract

Proteomics-based target identification of natural products affecting cancer metabolism

Muroi

Osada

2021

J Antibiot

View full text Add to dashboard Cite

A novel inhibitor of tumorspheres reveals the activation of the serine biosynthetic pathway upon mitochondrial inhibition

Cited by 5 publications

References 40 publications

Repurposing the Antidepressant Sertraline as SHMT Inhibitor to Suppress Serine/Glycine Synthesis–Addicted Breast Tumor Growth

Repurposing the Antidepressant Sertraline as SHMT Inhibitor to Suppress Serine/Glycine Synthesis–Addicted Breast Tumor Growth

Combined Targeted and Untargeted Profiling of HeLa Cells Deficient in Purine De Novo Synthesis

Proteomics-based target identification of natural products affecting cancer metabolism

Contact Info

Product

Resources

About