Propylselen inhibits cancer cell growth by targeting glutamate dehydrogenase at the NADP+ binding site

Hou, Wenhua; Lu, Shiying; Zhao, Han; Yu, Yan; Xu, Haodong; Yu, Biao; Su, Lin; Chen-shui, Lin; Ruan, Benfang

doi:10.1016/j.bbrc.2018.12.117

Cited by 11 publications

(10 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Further, many reported small-molecule inhibitors target several metabolic enzymes with similar structures, for example, EGCG targets both NADPH-dependent FASN and NADP + -dependent GDH. 21,187 The functions can be also markedly different among the isoforms of these enzymes. For instance, cytosolic ALDH1L1 mainly regulates reduced synthesis, while mitochondrial ALDH1L2 produces NADPH to attenuate oxidative stress.…”

Section: Discussionmentioning

confidence: 99%

“…74,186 For the glutamine metabolism pathway, ebselen, epigallocatechin-3-Gallate (EGCG), and propylselen are reported to bind to GDH-active sites to abolish NADP + binding and impair in cancer cell functions. 187 A study also shows that purpurin and its analog, R162, acting as mixed model inhibitors of GDH1, inhibit GDH1 activity, elevate ROS levels and thus attenuate cancer cell proliferation. 151 For the NADPH-synthesis enzymes involved in anapleurotic reactions, including IDH1/2, ME1/2/3, and CPT1/2, the targeting inhibitors are also being extensively developed.…”

Section: Fatty Acid Oxidationmentioning

confidence: 99%

“…Cell Biol. 17, 1484–1496 (2015) MTHFDs LY345899 Colorectal cancer 10 μM ~12 μM (SW620, 72 h) >200 μM (CCD-112, 72 h) 74 MTHFD2 DS18561882 Breast cancer 140 nM 140 nM (MDA-MB-231, 24 h) Not available 186 GDHs Propylselen Lung cancer cells 0–10 μM 3.4 μM (A549, 48 h) Not available 187 R162 Non-small cell lung carcinoma 20–40 μM 10 μM (KG1a, 48 h) >40 μM (MRC-5, HFF, 48 h) 151 IDH1 GSK864 Glioma 5–100 μM 5 μM (LN382, 48 h) Not available 125 IDH2 AGI-6780 Non-small cell lung carcinoma 0–50 μM ~5 μM (A549, 24 h) >50 μM (MRC-5, 48 h) 134 ME1 Piperazine-1-pyrrolidine-2,5-dione Colorectal cancer 50 μM <50 μM (HCT116, 24 h) >50 μM (IEC6, 24 h) 90 ME2 Embonic acid Non-small cell lung carcinoma 1–10 μM 1.4 μM (H1299, 48 h) Not available 189 CPTs Perhexiline Colorectal cancer 10–40 μM <20 μM (HCT116, 24 h) >20 μM (CCD841, 24 h) 167 CPT1 Etomoxir Prostate cancer 50–200 μM <75 μM (VCaP, 48 h) >75 μM (BPH-1, 48 h) Mol. Cancer Ther.…”

Section: Therapeutic Implications For Targeting Nadph Metabolismmentioning

confidence: 99%

See 2 more Smart Citations

NADPH homeostasis in cancer: functions, mechanisms and therapeutic implications

Lin

Tian

et al. 2020

Sig Transduct Target Ther

263

196

View full text Add to dashboard Cite

Nicotinamide adenine dinucleotide phosphate (NADPH) is an essential electron donor in all organisms, and provides the reducing power for anabolic reactions and redox balance. NADPH homeostasis is regulated by varied signaling pathways and several metabolic enzymes that undergo adaptive alteration in cancer cells. The metabolic reprogramming of NADPH renders cancer cells both highly dependent on this metabolic network for antioxidant capacity and more susceptible to oxidative stress. Modulating the unique NADPH homeostasis of cancer cells might be an effective strategy to eliminate these cells. In this review, we summarize the current existing literatures on NADPH homeostasis, including its biological functions, regulatory mechanisms and the corresponding therapeutic interventions in human cancers, providing insights into therapeutic implications of targeting NADPH metabolism and the associated mechanism for cancer therapy.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Fatty Acid Oxidationmentioning

confidence: 99%

Section: Therapeutic Implications For Targeting Nadph Metabolismmentioning

confidence: 99%

See 1 more Smart Citation

NADPH homeostasis in cancer: functions, mechanisms and therapeutic implications

Lin

Tian

et al. 2020

Sig Transduct Target Ther

263

196

View full text Add to dashboard Cite

show abstract

“…In this context, the identification of possible inhibitors of hGDH1 could be a strategy to modulate cancer cell growth and proliferation. Few compounds have been reported as inhibitors of hGDH among which phenol derivatives, as Epigallocatechin gallate (EGCG) [ 17 ] and chlorogenic acid [ 18 ], or Ebselen and Propylselen [ 16 , 19 ].…”

Section: Discussionmentioning

confidence: 99%

“…It was reported that phenol derivatives, as Epigallocatechin gallate (EGCG) [ 17 ] and chlorogenic acid [ 18 ] or synthetic organoselenium compounds, as Ebselen and Propylselen [ 19 ] inhibited hGDH.…”

Section: Introductionmentioning

confidence: 99%

Mitochondria-Mediated Apoptosis of HCC Cells Triggered by Knockdown of Glutamate Dehydrogenase 1: Perspective for Its Inhibition through Quercetin and Permethylated Anigopreissin A

et al. 2021

View full text Add to dashboard Cite

Metabolic reprogramming is a hallmark of cancer cells required to ensure high energy needs and the maintenance of redox balance. A relevant metabolic change of cancer cell bioenergetics is the increase in glutamine metabolism. Hepatocellular carcinoma (HCC), one of the most lethal cancer and which requires the continuous development of new therapeutic strategies, shows an up-regulation of human glutamate dehydrogenase 1 (hGDH1). GDH1 function may be relevant in cancer cells (or HCC) to drive the glutamine catabolism from L-glutamate towards the synthesis of α-ketoglutarate (α-KG), thus supplying key tricarboxylic acid cycle (TCA cycle) metabolites. Here, the effects of hGLUD1 gene silencing (siGLUD1) and GDH1 inhibition were evaluated. Our results demonstrate that siGLUD1 in HepG2 cells induces a significant reduction in cell proliferation (58.8% ± 10.63%), a decrease in BCL2 expression levels, mitochondrial mass (75% ± 5.89%), mitochondrial membrane potential (30% ± 7.06%), and a significant increase in mitochondrial superoxide anion (25% ± 6.55%) compared to control/untreated cells. The inhibition strategy leads us to identify two possible inhibitors of hGDH1: quercetin and Permethylated Anigopreissin A (PAA). These findings suggest that hGDH1 could be a potential candidate target to impair the metabolic reprogramming of HCC cells.

show abstract

Macrophage metabolism reprogramming EGCG-Cu coordination capsules delivered in polyzwitterionic hydrogel for burn wound healing and regeneration

Song

et al. 2023

Bioactive Materials

View full text Add to dashboard Cite

Propylselen inhibits cancer cell growth by targeting glutamate dehydrogenase at the NADP+ binding site

Cited by 11 publications

References 16 publications

NADPH homeostasis in cancer: functions, mechanisms and therapeutic implications

NADPH homeostasis in cancer: functions, mechanisms and therapeutic implications

Mitochondria-Mediated Apoptosis of HCC Cells Triggered by Knockdown of Glutamate Dehydrogenase 1: Perspective for Its Inhibition through Quercetin and Permethylated Anigopreissin A

Macrophage metabolism reprogramming EGCG-Cu coordination capsules delivered in polyzwitterionic hydrogel for burn wound healing and regeneration

Contact Info

Product

Resources

About