scholarly journals Dual Targeting of the Warburg Effect with a Glucose-Conjugated Lactate Dehydrogenase Inhibitor

ChemBioChem ◽  
2013 ◽  
Vol 14 (17) ◽  
pp. 2263-2267 ◽  
Author(s):  
Emilia C. Calvaresi ◽  
Carlotta Granchi ◽  
Tiziano Tuccinardi ◽  
Valeria Di Bussolo ◽  
Robert W. Huigens ◽  
...  
Keyword(s):  
Lactate Dehydrogenase ◽  
Warburg Effect ◽  
Dual Targeting ◽  
The Warburg Effect ◽  
Lactate Dehydrogenase Inhibitor

The tumor suppressor folliculin inhibits lactate dehydrogenase A and regulates the Warburg effect

2021 ◽  
Vol 28 (8) ◽  
pp. 662-670
Author(s):  
Mark R. Woodford ◽  
Alexander J. Baker-Williams ◽  
Rebecca A. Sager ◽  
Sarah J. Backe ◽  
Adam R. Blanden ◽  
...  
Keyword(s):  
Lactate Dehydrogenase ◽  
Tumor Suppressor ◽  
Warburg Effect ◽  
The Warburg Effect

Structural and functional regulation of lactate dehydrogenase-A in cancer

2020 ◽  
Vol 12 (5) ◽  
pp. 439-455 ◽  
Author(s):  
Mark R Woodford ◽  
Victor Z Chen ◽  
Sarah J Backe ◽  
Gennady Bratslavsky ◽  
Mehdi Mollapour
Keyword(s):  
Lactate Dehydrogenase ◽  
Oxidative Phosphorylation ◽  
Warburg Effect ◽  
Recent Progress ◽  
Therapeutic Option ◽  
Hallmarks Of Cancer ◽  
Physiological Conditions ◽  
Functional Regulation ◽  
Dramatic Shift ◽  
The Warburg Effect

Dysregulated metabolism is one of the hallmarks of cancer. Under normal physiological conditions, ATP is primarily generated by oxidative phosphorylation. Cancers commonly undergo a dramatic shift toward glycolysis, despite the presence of oxygen. This phenomenon is known as the Warburg effect, and requires the activity of LDHA. LDHA converts pyruvate to lactate in the final step of glycolysis and is often upregulated in cancer. LDHA inhibitors present a promising therapeutic option, as LDHA blockade leads to apoptosis in cancer cells. Despite this, existing LDHA inhibitors have shown limited clinical efficacy. Here, we review recent progress in LDHA structure, function and regulation as well as strategies to target this critical enzyme.

scholarly journals Suppression of lactate dehydrogenase A compromises tumor progression by downregulation of the Warburg effect in glioblastoma

Neuroreport ◽  
2016 ◽  
Vol 27 (2) ◽  
pp. 110-115 ◽  
Author(s):  
Juan Li ◽  
Shuchai Zhu ◽  
Jing Tong ◽  
Hui Hao ◽  
Jie Yang ◽  
...  
Keyword(s):  
Lactate Dehydrogenase ◽  
Tumor Progression ◽  
Warburg Effect ◽  
The Warburg Effect

The warburg effect and tumour cell survival in human GBMs

2007 ◽  
Vol 30 (4) ◽  
pp. 97 ◽  
Author(s):  
A Wolf ◽  
J Mukherjee ◽  
A Guha
Keyword(s):  
Cytochrome C ◽  
Cell Survival ◽  
Expression Profile ◽  
Tumour Cell ◽  
Warburg Effect ◽  
Glycolytic Enzymes ◽  
Cytochrome C Release ◽  
Apoptotic Pathway ◽  
The Warburg Effect

Introduction: GBMs are resistant to apoptosis induced by the hypoxic microenvironment and standard therapies including radiation and chemotherapy. We postulate that the Warburg effect, a preferential glycolytic phenotype of tumor cells even under aerobic conditions, plays a role in these aberrant pro-survival signals. In this study we quantitatively examined the expression profile of hypoxia-related glycolytic genes within pathologically- and MRI-defined “centre” and “periphery” of GBMs. We hypothesize that expression of hypoxia-induced glycolytic genes, particularly hexokinase 2 (HK2), favours cell survival and modulates resistance to tumour cell apoptosis by inhibiting the intrinsic mitochondrial apoptotic pathway. Methods: GBM patients underwent conventional T1-weighted contrast-enhanced MRI and MR spectroscopy studies on a 3.0T GE scanner, prior to stereotactic sampling (formalin and frozen) from regions which were T1-Gad enhancing (“centre”) and T2-positive, T1-Gad negative (“periphery”). Real-time qRT-PCR was performed to quantify regional gene expression of glycolytic genes including HK2. In vitro functional studies were performed in U87 and U373 GBM cell lines grown in normoxic (21% pO2) and hypoxic (< 1%pO2) conditions, transfected with HK2 siRNA followed by measurement of cell proliferation (BrdU), apoptosis (activated caspase 3/7, TUNEL, cytochrome c release) and viability (MTS assay). Results: There exists a differential expression profile of glycolytic enzymes between the hypoxic center and relatively normoxic periphery of GBMs. Under hypoxic conditions, there is increased expression of HK2 at the mitochondrial membrane in GBM cells. In vitro HK2 knockdown led to decreased cell survival and increased apoptosis via the intrinsic mitochondrial pathway, as seen by increased mitochondrial release of cytochrome-C. Conclusions: Increased expression of HK2 in the centre of GBMs promotes cell survival and confers resistance to apoptosis, as confirmed by in vitro studies. In vivo intracranial xenograft studies with injection of HK2-shRNA are currently being performed. HK2 and possibly other glycolytic enzymes may provide a target for enhanced therapeutic responsiveness thereby improving prognosis of patients with GBMs.

Phytometabolites Targeting the Warburg Effect in Cancer Cells: A Mechanistic Review

2017 ◽  
Vol 18 (9) ◽  
Author(s):  
Mohadeseh Hasanpourghadi ◽  
Chung Yeng Looi ◽  
Ashok Kumar Pandurangan ◽  
Gautam Sethi ◽  
Won Fen Wong ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Warburg Effect ◽  
The Warburg Effect

Metabolic reprogramming for cancer cells and their microenvironment: Beyond the Warburg Effect

2018 ◽  
Vol 1870 (1) ◽  
pp. 51-66 ◽  
Author(s):  
Linchong Sun ◽  
Caixia Suo ◽  
Shi-ting Li ◽  
Huafeng Zhang ◽  
Ping Gao
Keyword(s):  
Cancer Cells ◽  
Warburg Effect ◽  
Metabolic Reprogramming ◽  
The Warburg Effect
Sign in / Sign up

Export Citation Format

Share Document