scholarly journals The Multifarious Functions of Pyruvate Kinase M2 in Oral Cancer Cells

2018 ◽  
Vol 19 (10) ◽  
pp. 2907 ◽  
Author(s):  
Miyako Kurihara-Shimomura ◽  
Tomonori Sasahira ◽  
Chie Nakashima ◽  
Hiroki Kuniyasu ◽  
Hiroyuki Shimomura ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Pyruvate Kinase ◽  
Energy Flow ◽  
Aerobic Glycolysis ◽  
High Energy ◽  
Strongly Correlated ◽  
Mucosal Cells ◽  
Oral Cancer Cells ◽  
And Function

Head and neck cancers, including oral squamous cell carcinoma (OSCC), are the sixth most common malignancies worldwide. OSCC frequently leads to oral dysfunction, which worsens a patient’s quality of life. Moreover, its prognosis remains poor. Unlike normal cells, tumor cells preferentially metabolize glucose by aerobic glycolysis. Pyruvate kinase (PK) catalyzes the final step in glycolysis, and the transition from PKM1 to PKM2 is observed in many cancer cells. However, little is known about PKM expression and function in OSCC. In this study, we investigated the expression of PKM in OSCC specimens and performed a functional analysis of human OSCC cells. We found that the PKM2/PKM1 ratio was higher in OSCC cells than in adjacent normal mucosal cells and in samples obtained from dysplasia patients. Furthermore, PKM2 expression was strongly correlated with OSCC tumor progression on immunohistochemistry. PKM2 expression was higher during cell growth, invasion, and apoptosis in HSC3 cells, which show a high energy flow and whose metabolism depends on aerobic glycolysis and oxidative phosphorylation. PKM2 expression was also associated with the production of reactive oxygen species (ROS) and integration of glutamine into lactate. Our results suggested that PKM2 has a variety of tumor progressive functions in OSCC cells.

scholarly journals Berberine Inhibited the Proliferation of Cancer Cells by Suppressing the Activity of Tumor Pyruvate Kinase M2

2017 ◽  
Vol 12 (9) ◽  
pp. 1934578X1701200
Author(s):  
Zhichao Li ◽  
Hanqing Li ◽  
Yangxu Lu ◽  
Peng Yang ◽  
Zhuoyu Li
Keyword(s):  
Cancer Cells ◽  
Pyruvate Kinase ◽  
Aerobic Glycolysis ◽  
Isoquinoline Alkaloid ◽  
Therapeutic Drug ◽  
Pyruvate Kinase M2 ◽  
Anticancer Properties ◽  
Key Enzyme ◽  
Hct 116 ◽  
Dynamic Fluorescence

Berberine, an isoquinoline alkaloid extracted from coptis, exerts anti-proliferation and anticancer properties. Pyruvate kinase M2 (PKM2) is a key enzyme of aerobic glycolysis and considered as the potential anticancer target. However, the inhibition effects and interaction action between Berberine and PKM2 is not well known. In this study, berberine showed antitumor activity of HCT-116 and HeLa cells with the suppression of cell proliferation. Moreover, berberine inhibited the enzyme activity of PKM2 in cancer cells, but had no impact on PKM2 expression. Further research showed that the interaction between berberine and PKM2 was dynamic fluorescence quenching and the main intermolecular force was hydrogen bonding. These findings revealed that berberine may serve as a therapeutic drug for cancer chemotherapy.

scholarly journals Oleanolic Acid Suppresses Aerobic Glycolysis in Cancer Cells by Switching Pyruvate Kinase Type M Isoforms

PLoS ONE ◽  
2014 ◽  
Vol 9 (3) ◽  
pp. e91606 ◽  
Author(s):  
Jia Liu ◽  
Ning Wu ◽  
Leina Ma ◽  
Ming Liu ◽  
Ge Liu ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Pyruvate Kinase ◽  
Oleanolic Acid ◽  
Aerobic Glycolysis

scholarly journals Dihydropyrimidinase Like 2 Promotes Bladder Cancer Progression via Pyruvate Kinase M2-Induced Aerobic Glycolysis and Epithelial–Mesenchymal Transition

2021 ◽  
Vol 9 ◽  
Author(s):  
Jun Zou ◽  
Ruiyan Huang ◽  
Yanfei Chen ◽  
Xiaoping Huang ◽  
Huajun Li ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cancer Cells ◽  
Pyruvate Kinase ◽  
Cancer Progression ◽  
Epithelial Mesenchymal Transition ◽  
Aerobic Glycolysis ◽  
Mesenchymal Transition ◽  
Bladder Cancer Cells ◽  
Malignant Behavior

BackgroundAerobic glycolysis and epidermal–mesenchymal transition (EMT) play key roles in the development of bladder cancer. This study aimed to investigate the function and the underlying mechanism of dihydropyrimidinase like 2 (DPYSL2) in bladder cancer progression.MethodsThe expression pattern of DPYSL2 in bladder cancer and the correlation of DPYSL2 expression with clinicopathological characteristics of bladder cancer patients were analyzed using the data from different databases and tissue microarray. Gain- and loss-of-function assays were performed to explore the role of DPYSL2 in bladder cancer progression in vitro and in mice. Proteomic analysis was performed to identify the interacting partner of DPYSL2 in bladder cancer cells.FindingsThe results showed that DPYSL2 expression was upregulated in bladder cancer tissue compared with adjacent normal bladder tissue and in more aggressive cancer stages compared with lower stages. DPYSL2 promoted malignant behavior of bladder cancer cells in vitro, as well as tumor growth and distant metastasis in mice. Mechanistically, DPYSL2 interacted with pyruvate kinase M2 (PKM2) and promoted the conversion of PKM2 tetramers to PKM2 dimers. Knockdown of PKM2 completely blocked DPYSL2-induced enhancement of the malignant behavior, glucose uptake, lactic acid production, and epithelial–mesenchymal transition in bladder cancer cells.InterpretationIn conclusion, the results suggest that DPYSL2 promotes aerobic glycolysis and EMT in bladder cancer via PKM2, serving as a potential therapeutic target for bladder cancer treatment.

Cellular Bioenergetics in Lymphoid Neoplasia

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. SCI-25-SCI-25 ◽  
Author(s):  
Matthew Vander Heiden
Keyword(s):  
Cancer Cells ◽  
Pyruvate Kinase ◽  
Cell Biology ◽  
Aerobic Glycolysis ◽  
Lactate Production ◽  
Proliferating Cells ◽  
Hematopoietic Stem ◽  
Oxygen Levels ◽  
Lymphoid Neoplasia

Abstract Abstract SCI-25 Many cancer cells metabolize glucose by aerobic glycolysis, a phenomenon characterized by increased glycolysis with lactate production and decreased oxidative phosphorylation. We have argued that alterations in cell metabolism associated with cancer may be selected by cancer cells to meet the distinct metabolic needs of proliferation. Unlike metabolism in differentiated cells, which is geared toward efficient ATP generation, the metabolism in cancer cells must be adapted to facilitate the accumulation of biomass. Cancer cells divert a larger fraction of their nutrient metabolism to pathways other than mitochondrial respiration regardless of oxygen availability. Nevertheless, oxygen levels still influence how nutrients are metabolized. We have found that the source of carbon used in various anabolic processes varies based on oxygen levels. Furthermore, the enzymes used to metabolize nutrients can also differ based on the cellular context. This includes regulation of isocitrate dehydrogenase, an enzyme that is mutated in some cancers. There is also strong selection for use of the M2 isoform of pyruvate kinase (PK-M2) to metabolize glucose in cancer cell lines. However, evidence from mouse models suggests that PK-M2 is dispensable for glucose metabolism by many tumors in vivo, suggesting an alternate pathway to convert phosphoenolpyruvate to pyruvate can be used to metabolize glucose. This regulation of pyruvate kinase also plays an important role in hematopoietic stem cell biology. Together, these findings argue that distinct metabolic phenotypes exist among proliferating cells, and both environmental and genetic factors influence how metabolism is regulated to support cell growth. Disclosures: Vander Heiden: Agios Pharmaceuticals: Consultancy, Equity Ownership.

Characterization of β-Cyclodextrin-Thymol Inclusion Complexes

2011 ◽  
Vol 233-235 ◽  
pp. 1766-1773
Author(s):  
Xiang Hua Chai ◽  
Ruo Hui Lin ◽  
Ke Gang Wu ◽  
Shu Ri Li
Keyword(s):  
Inclusion Complexes ◽  
Water Solution ◽  
Molecular Size ◽  
High Energy ◽  
Saturated Water Solution ◽  
Quality Of Food ◽  
And Function ◽  
Type Crystal

Thymol had been confirmed to be applied to prevent the growth of bacteria and function as an antioxidant to maintain the quality of food products. It is known that a number of components of essential oils including thymol are suitable to form inclusion complexes with β-Cyclodextrin, since they fit the hydrophobic cavity tightly. The β-cyclodextrin-thymol(β-CD-thymol) inclusion complexes were prepared by the saturated water solution method. SEM results showed that the lattice of β-CD-thymol inclusions was different from hydrogen-bond-type crystal lattice of β-CD and β-CD-water inclusions; the disappearance of high-energy water molecules in the β-CD cavity was observed from SAT data; the aromatic ring of the thymol was included in the β-CD cavity, according to the FTIR data. Besides, according to the calculation of chemical structure, molecular size of thymol was estimated. These results supported a successful formation of the inclusion and the preliminary structure of host-guest inclusions was constructed, indicating the -CH3 is close to the β-CD narrower rim, while the -CH2 and OH group is close to the wide one.

Boronic acid derivative activates pyruvate kinase M2 indispensable for redox metabolism in oral cancer cells

2022 ◽  
pp. 128539
Author(s):  
Mohd Rihan ◽  
Lakshmi Vineela Nalla ◽  
Anil Dharavath ◽  
Sagarkumar Patel ◽  
Amit Shard ◽  
...  
Keyword(s):  
Oral Cancer ◽  
Cancer Cells ◽  
Pyruvate Kinase ◽  
Acid Derivative ◽  
Boronic Acid ◽  
Redox Metabolism ◽  
Pyruvate Kinase M2 ◽  
Oral Cancer Cells

scholarly journals A novel transcript variant of proteasome activator 28γ: Identification and function in oral cancer cells

2015 ◽  
Vol 47 (1) ◽  
pp. 188-194 ◽  
Author(s):  
XIAOPING XU ◽  
DONGJUAN LIU ◽  
NING JI ◽  
TAIWEN LI ◽  
LONGJIANG LI ◽  
...  
Keyword(s):  
Oral Cancer ◽  
Cancer Cells ◽  
Transcript Variant ◽  
Proteasome Activator ◽  
Novel Transcript ◽  
Oral Cancer Cells ◽  
And Function

scholarly journals Pyruvate kinase M2-specific siRNA induces apoptosis and tumor regression

2012 ◽  
Vol 209 (2) ◽  
pp. 217-224 ◽  
Author(s):  
Michael S. Goldberg ◽  
Phillip A. Sharp
Keyword(s):  
Cancer Cells ◽  
Pyruvate Kinase ◽  
Tumor Regression ◽  
Aerobic Glycolysis ◽  
Cell Metabolism ◽  
Cell Types ◽  
Multiple Cancer ◽  
Selective Growth Advantage ◽  
Promising Target

The development of cancer-specific therapeutics has been limited because most healthy cells and cancer cells depend on common pathways. Pyruvate kinase (PK) exists in M1 (PKM1) and M2 (PKM2) isoforms. PKM2, whose expression in cancer cells results in aerobic glycolysis and is suggested to bestow a selective growth advantage, is a promising target. Because many oncogenes impart a common alteration in cell metabolism, inhibition of the M2 isoform might be of broad applicability. We show that several small interfering (si) RNAs designed to target mismatches between the M2 and M1 isoforms confer specific knockdown of the former, resulting in decreased viability and increased apoptosis in multiple cancer cell lines but less so in normal fibroblasts or endothelial cells. In vivo delivery of siPKM2 additionally causes substantial tumor regression of established xenografts. Our results suggest that the inherent nucleotide-level specificity of siRNA can be harnessed to develop therapeutics that target isoform-specific exons in genes exhibiting differential splicing patterns in various cell types.

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