scholarly journals The decrease of glycolytic enzyme hexokinase 1 accelerates tumor malignancy via deregulating energy metabolism but sensitizes cancer cells to 2-deoxyglucose inhibition

Oncotarget ◽  
2018 ◽  
Vol 9 (27) ◽  
pp. 18949-18969 ◽  
Author(s):  
Po-Lin Tseng ◽  
Chih-Wei Chen ◽  
Keng-Hsun Hu ◽  
Hung-Chi Cheng ◽  
Yuan-Ho Lin ◽  
...  
Keyword(s):  
Energy Metabolism ◽  
Cancer Cells ◽  
Glycolytic Enzyme

scholarly journals Expression of sperm-specific glyceraldehyde-3-phosphate dehydrogenase in melanoma cells changes their energy metabolism

2020 ◽  
Vol 66 (5) ◽  
pp. 372-377
Author(s):  
A.K. Melnikova ◽  
M.L. Kuravsky ◽  
K.V. Kulikova ◽  
I.A. Sevostyanova ◽  
V.I. Muronetz
Keyword(s):  
Energy Metabolism ◽  
Glucose Uptake ◽  
Cancer Cells ◽  
Cell Lines ◽  
Lactate Production ◽  
Melanoma Cells ◽  
Glycolytic Enzyme ◽  
Glucose Uptake Rate ◽  
Lower Glucose ◽  
Induction Of Apoptosis

The somatic isoform of the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH; EC1.2.1.12) is involved in such crucial for cancer cells development pathways as induction of apoptosis and glycolytic regulation. At the same time, sperm-specific isoform (GAPDHS) does not exhibit all the same functions as somatic enzyme. The expression of sperm-specific GAPDH without N-terminal domain in some melanoma cells along with somatic isoenzyme, shown in our previous work, has led to the proposal of this unusual enzyme's possible role in regulation of cancer cells glycolysis. In the presented work we have tested production of GAPDHS in 13 additional melanoma cell lines by immunoblotting. We have also gathered data on energy metabolism in 5 selected cell lines by evaluation of glucose uptake and lactate production in differing conditions. We have demonstrated that in standard cultivation media glucose uptake by MelP cells, producing substantial amounts of GAPDHS protein was higher than in MelKor cells, producing lesser amounts of GAPDHS. All other analyzed cell lines that do not produce GAPDHS (MelMS, MelSi and Malme3M) had even a lower glucose uptake rate.

734 A novel NQO1 specific anti-tumor agent, SBSC-S3001, selectively regresses the growth of tumors with high NQO1 expression

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A778-A778
Author(s):  
Minhyuk Yun ◽  
Goo-Young Kim ◽  
Sang Woo Jo ◽  
Changhoon In ◽  
Gyu-Young Moon ◽  
...  
Keyword(s):  
Energy Metabolism ◽  
Cancer Cells ◽  
Poor Prognosis ◽  
High Expression ◽  
List Type ◽  
Dependent Manner ◽  
Breast Cancers ◽  
Quinone Oxidoreductase ◽  
Key Enzymes

BackgroundNAD(P)H-quinone oxidoreductase 1 (NQO1) is a cytosolic two-electron oxidoreductase overexpressed in many types of cancers, including breast cancer, pancreatic cancer, colorectal cancer, cholangiocarcinoma, uterine cervical cancer, melanoma, and lung cancer.1Up-regulation of NQO1 protects cells from oxidative stress and various cytotoxic quinones and is associated with late clinical stage, poor prognosis and lymph node metastasis.2 3 NQO1 increases stability of HIF-1α protein, which has been implicated in survival, proliferation, and malignance of cancer.1 Therefore, accumulating evidences suggest NQO1 as a promising therapeutic target for cancer. Accordingly, we have characterized the effect of a novel synthetic NQO1 substrate SBSC-S3001, and demonstrated its selective cytotoxic effects in cancer cells with high expression of NQO1.MethodsIn vitro cytotoxicity was determined by sulforhodamine B (SRB) assay in cancer cells with high NQO1 expression and CRISPR-mediated NQO1 knockout cells. The effect of SBSC-S3001 on the energy metabolism pathway was evaluated by western blot analysis of metabolism associated proteins from NQO1-overexpressed cancer cells treated with the compound for 24 hours. In vivo anti-tumor activity was evaluated in MC38 syngeneic and DLD-1 orthotopic mice models.ResultsSBSC-S3001 exhibited selective cytotoxicity in cancer cells with high expression of NQO1 in a dose-dependent manner. The cytotoxicity was observed in both normoxia and hypoxia conditions, correlating with the energy metabolism, mitochondrial biogenesis, and cancer proliferative pathways. Also, stronger cytotoxicity was observed in NQO1-overexpressed cancer cells treated with SBSC-S3001 compared to beta-lapachone and analogue treatment.4 When evaluated in vivo, SBSC-S3001 effectively inhibited the growth of syngeneic and orthotopic tumors when administered as a monotherapy. SBSC-S3001 treatment associated with reduction in key enzymes of the glycolytic pathway (LDHa and GAPDH) and HIF-1α and increase in levels of mitochondrial oxidative phosphorylation (OXPHOS) complex.ConclusionsTreatment of SBSC-S3001, a novel, NQO1-specific substrate reduces HIF-1α and key enzymes associated with glycolysis and suppresses the growth of tumors overexpressing NQO1. Further characterization of SBSC-S3001 as a novel metabolic anti-cancer agent for cancers with NQO1 overexpression is warranted.Ethics ApprovalThe study was approved by Samyang Biopharmaceuticals Institution’s Ethics Board, approval number SYAU2031.ReferencesOh ET, Kim JW, Kim JMet. al., NQO1 inhibits proteasome-mediated degradation of HIF-1α. Nat Commun 2016; 14:13593.Ma, Y. et al. NQO1 overexpression is associated with poor prognosis in squamous cell carcinoma of the uterine cervix. BMC Cancer 2014;14: 414Yang, Y. et al. Clinical implications of high NQO1 expression in breast cancers. J. Exp. Clin. Cancer Res 2014;33:144.Yang Y, Zhou X, Xu M, et al., β-lapachone suppresses tumour progression by inhibiting epithelial-to-mesenchymal transition in NQO1-positive breast cancers. Sci Rep 2017;7:2681.

scholarly journals MDM2 ubiquitin-ligase down-regulate energy metabolism of cancer cells

2019 ◽  
Vol 35 (3) ◽  
pp. 233-233
Author(s):  
O. Shuvalov ◽  
A. Petukhov ◽  
O. Fedorova ◽  
A. Daks ◽  
E. Baidyuk ◽  
...  
Keyword(s):  
Energy Metabolism ◽  
Cancer Cells ◽  
Ubiquitin Ligase ◽  
Regulate Energy Metabolism

scholarly journals Cellular Mechanisms of Metabolic Remodeling During Fluid Sheer Stress-Induced Metastasis

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 322-322
Author(s):  
Tracie Dunn ◽  
Spenser Brown ◽  
Nelli Mnatsakanyan ◽  
Elizabeth Jonas ◽  
Kim Yonghyun ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Energy Metabolism ◽  
Cancer Cells ◽  
Atp Synthase ◽  
Breast Cancer Cells ◽  
Transport Systems ◽  
Cellular Mechanisms ◽  
Sheer Stress ◽  
Metabolic Remodeling ◽  
C Subunit

Abstract Objectives Fluid sheer stress (FSS) is a physical stimuli of circulating tumor cells responsible for development of and progression to cancer. FSS is reported to enhance chemoresistance and proliferation in breast cancer cells. However, cellular mechanisms explaining how FSS contributes to the metastatic phenotype of breast cancer cell are less known. Chemoresistance is highly dependent upon active transport systems, and cell division and growth require ATP. In this study, we hypothesize that FSS contributes to mitochondrial remodeling and leads to alterations in energy metabolism which favor metastasis. Methods MDA-MB-231 human breast cancer cells were exposed to fluid sheer stress (FSS). MDA-MB-231 cells were then grown in culture media for 24 h, and intracellular energy (ATP) and abundance of ATP synthase were analyzed. Results FSS significantly increases intracellular ATP in MDA-MB-231 breast cancer cells. Interestingly, MDA-MB-231 cells retained increased ATP after treatment with the uncoupler FCCP indicating remodeling and decreased reliance on mitochondrial energy metabolism. We then quantified the abundance of ATP synthase, the key enzyme complex that produces mitochondrial ATP. FSS significantly decreased protein levels of the c-subunit of ATP synthase. Conclusions Our data show that FSS causes metabolic remodeling of mitochondria-dependent ATP production. We suggest that the c-subunit of ATP synthase is an important target of FSS-mediated metastasis. Strategies to enhance the abundance or activity of the c-subunit may prevent metabolic remodeling-associated with metastasis in FSS-exposed circulating cancer cells. Funding Sources Alabama Life Research Institute (ALRI) 14,565.

STAT3 modulates the energy metabolism of ovarian cancer cells

2018 ◽  
Vol 149 ◽  
pp. 48
Author(s):  
R. Rattan ◽  
V. Raja ◽  
N. Rasool ◽  
M.A. Elshaikh ◽  
A.R. Munkarah ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Energy Metabolism ◽  
Cancer Cells ◽  
Ovarian Cancer Cells
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