scholarly journals Biological Evaluation of Oxindole Derivative as a Novel Anticancer Agent against Human Kidney Carcinoma Cells

Biomolecules ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 1260
Author(s):  
Prasanta Dey ◽  
Amit Kundu ◽  
Sang Hoon Han ◽  
Kyeong-Seok Kim ◽  
Jae Hyeon Park ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Renal Cancer ◽  
Glucose Transporter ◽  
Tumor Development ◽  
Xenograft Model ◽  
Human Kidney ◽  
Biological Evaluation ◽  
Glucose Transporter 1 ◽  
Cycle Arrest ◽  
The Usa

Renal cell carcinoma has emerged as one of the leading causes of cancer-related deaths in the USA. Here, we examined the anticancer profile of oxindole derivatives (SH-859) in human renal cancer cells. Targeting 786-O cells by SH-859 inhibited cell growth and affected the protein kinase B/mechanistic target of rapamycin 1 pathway, which in turn downregulated the expression of glycolytic enzymes, including lactate dehydrogenase A and glucose transporter-1, as well as other signaling proteins. Treatment with SH-859 altered glycolysis, mitochondrial function, and levels of adenosine triphosphate and cellular metabolites. Flow cytometry revealed the induction of apoptosis and G0/G1 cell cycle arrest in renal cancer cells following SH-859 treatment. Induction of autophagy was also confirmed after SH-859 treatment by acridine orange and monodansylcadaverine staining, immunocytochemistry, and Western blot analyses. Finally, SH-859 also inhibited the tumor development in a xenograft model. Thus, SH-859 can serve as a potential molecule for the treatment of human renal carcinoma.

scholarly journals Knockdown of Pyruvate Kinase M2 Inhibits Cell Proliferation, Metabolism, and Migration in Renal Cell Carcinoma

2019 ◽  
Vol 20 (22) ◽  
pp. 5622 ◽  
Author(s):  
Dey ◽  
Son ◽  
Kundu ◽  
Kim ◽  
Lee ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Pyruvate Kinase ◽  
Renal Cancer ◽  
Glucose Transporter ◽  
Migration And Invasion ◽  
Metabolite Formation ◽  
Glucose Transporter 1 ◽  
Pyruvate Kinase M2 ◽  
Downstream Signaling ◽  
And Migration

Emerging evidence indicates that the activity of pyruvate kinase M2 (PKM2) isoform is crucial for the survival of tumor cells. However, the molecular mechanism underlying the function of PKM2 in renal cancer is undetermined. Here, we reveal the overexpression of PKM2 in the proximal tubule of renal tumor tissues from 70 cases of patients with renal carcinoma. The functional role of PKM2 in human renal cancer cells following small-interfering RNA-mediated PKM2 knockdown, which retarded 786-O cell growth was examined. Targeting PKM2 affected the protein kinase B (AKT)/mechanistic target of the rapamycin 1 (mTOR) pathway, and downregulated the expression of glycolytic enzymes, including lactate dehydrogenase A and glucose transporter-1, and other downstream signaling key proteins. PKM2 knockdown changed glycolytic metabolism, mitochondrial function, adenosine triphosphate (ATP) level, and intracellular metabolite formation and significantly reduced 786-O cell migration and invasion. Acridine orange and monodansylcadaverine staining, immunocytochemistry, and immunoblotting analyses revealed the induction of autophagy in renal cancer cells following PKM2 knockdown. This is the first study to indicate PKM2/AKT/mTOR as an important regulatory axis mediating the changes in the metabolism of renal cancer cells.

Glycolysis Inhibition as a Strategy for Hepatocellular Carcinoma Treatment?

2018 ◽  
Vol 19 (1) ◽  
pp. 26-40 ◽  
Author(s):  
A.P. Alves ◽  
A.C. Mamede ◽  
M.G. Alves ◽  
P.F. Oliveira ◽  
S.M. Rocha ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cancer Cells ◽  
Anticancer Agents ◽  
Glucose Transporter ◽  
Public Health Problem ◽  
High Morbidity ◽  
Curative Intent ◽  
Malignant Liver Tumor ◽  
Glucose Transporter 1 ◽  
Inhibition Of Glycolysis

Hepatocellular carcinoma (HCC) is the most frequently detected primary malignant liver tumor, representing a worldwide public health problem due to its high morbidity and mortality rates. The HCC is commonly detected in advanced stage, precluding the use of treatments with curative intent. For this reason, it is crucial to find effective therapies for HCC. Cancer cells have a high dependence of glycolysis for ATP production, especially under hypoxic environment. Such dependence provides a reliable possible strategy to specifically target cancer cells based on the inhibition of glycolysis. HCC, such as other cancer types, presents a clinically well-known upregulation of several glycolytic key enzymes and proteins, including glucose transporters particularly glucose transporter 1 (GLUT1). Such enzymes and proteins constitute potential targets for therapy. Indeed, for some of these targets, several inhibitors were already reported, such as 2-Deoxyglucose, Imatinib or Flavonoids. Although the inhibition of glycolysis presents a great potential for an anticancer therapy, the development of glycolytic inhibitors as a new class of anticancer agents needs to be more explored. Herein, we propose to summarize, discuss and present an overview on the different approaches to inhibit the glycolytic metabolism in cancer cells, which may be very effective in the treatment of HCC.

scholarly journals Oncoprotein LAMTOR5 activates GLUT1 via upregulating NF-κB in liver cancer

Open Medicine ◽  
2019 ◽  
Vol 14 (1) ◽  
pp. 264-270 ◽  
Author(s):  
Jing Zhou ◽  
Yajun Li ◽  
Danhua Li ◽  
Zhi Liu ◽  
Jie Zhang
Keyword(s):  
Liver Cancer ◽  
Cancer Cells ◽  
Western Blotting ◽  
Glucose Transporter ◽  
Luciferase Reporter ◽  
Pcr Assay ◽  
Glucose Transporter 1 ◽  
Over Expression ◽  
Liver Cancer Cells ◽  
Reporter Assays

AbstractObjectiveAccumulating reports reveal that serving as an oncogenic factor LAMTOR5 is involved in the progression of many specific cancers. Glucose transporter 1 (GLUT1) is frequently identified in many cancers. However, it remains unexplored whether GLUT1 plays a role in LAMTOR5-enhanced liver cancer. Here, we aim to decipher the function of LAMTOR5 in the regulation of GLUT1 in liver cancer.MethodsThe effect of LAMTOR5 on GLUT1 was analyzed using Western blotting and RT-PCR assay. Dose-increased over-expression or silencing of LAMTOR5 was performed through transient transfection. LAMTOR5-activated GLUT1 promoter was revealed by luciferase reporter assay. The regulation of GLUT1 by LAMTOR5/NF-κB was examined via Western blotting and luciferase reporter assays.ResultsThe data showed that in liver cancer cells under the administration with dose-increased LAMTOR5, the level of mRNA and protein of GLUT1 was obviously raised. Our data revealed that the activities of GLUT1 promoter were induced by LAMTOR5. Then, we found that the elevation of GLUT 1 mediated by LAMTOR5 slowed when the inhibitor or siRNAs of NF-κB was introduced into the liver cancer cells. Conclusion. LAMTOR5 is responsible for the activation of GLUT1 via transcription factor NF-κB in liver cancer.

scholarly journals Up-regulation of key glycolysis proteins in cancer development

2018 ◽  
Vol 13 (1) ◽  
pp. 569-581
Author(s):  
Nicole Nowak ◽  
Anna Kulma ◽  
Jan Gutowicz
Keyword(s):  
Cancer Cells ◽  
Glucose Transporter ◽  
Lactate Production ◽  
Cancer Development ◽  
Glucose Transporter 1 ◽  
Expression Of Genes ◽  
Glycolysis Pathway ◽  
Cancer Cell Survival ◽  
Glycolytic Rate

AbstractIn rapid proliferating cancer cells, there is a need for fast ATP and lactate production, therefore cancer cells turn off oxidative phosphorylation and turn on the so called "Warburg effect". This regulating the expression of genes involved in glycolysis. According to many studies, glucose transporter 1, which supplies glucose to the cell, is the most abundantly expressed transporter in cancer cells. Hexokinase 2, is one of four hexokinase isoenzymes, is also another highly expressed enzyme in cancer cells and it functions to enhance the glycolytic rate. The up-regulation of these two proteins has been established as an important factor in promoting development and metastasis in many types of cancer. Furthermore, other enzymes involved in glycolysis pathway such as phosphoglucose isomerase and glyceraldehyde 3-phosphate dehydrogenase, exhibit additional functions in promoting tumor growth in a non-glycolytic way. This review demonstrates the pivotal role of GLUT1, HK2, PGI and GAPDH in cancer development. In particular, we look at how the multifunctional proteins, PGI and GAPDH, affect cancer cell survival. We also present various clinical cancer cases in terms of the overexpression of selected proteins, which may be considered as a therapeutic target.

scholarly journals Salicylketoximes That Target Glucose Transporter 1 Restrict Energy Supply to Lung Cancer Cells

ChemMedChem ◽  
2015 ◽  
Vol 10 (11) ◽  
pp. 1892-1900 ◽  
Author(s):  
Carlotta Granchi ◽  
Yanrong Qian ◽  
Hyang Yeon Lee ◽  
Ilaria Paterni ◽  
Carolina Pasero ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Energy Supply ◽  
Glucose Transporter ◽  
Lung Cancer Cells ◽  
Glucose Transporter 1 ◽  
Target Glucose

scholarly journals MicroRNA-124 suppresses proliferation and glycolysis in non–small cell lung cancer cells by targeting AKT–GLUT1/HKII

Tumor Biology ◽  
2017 ◽  
Vol 39 (5) ◽  
pp. 101042831770621 ◽  
Author(s):  
Xiaojian Zhao ◽  
Caiping Lu ◽  
Weiwei Chu ◽  
Bing Zhang ◽  
Qiang Zhen ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Energy Metabolism ◽  
Small Cell Lung Cancer ◽  
Cancer Cells ◽  
Cell Lung Cancer ◽  
Glucose Transporter ◽  
Small Cell ◽  
Small Cell Lung ◽  
Glucose Transporter 1

Non–small cell lung cancer accounts for 85% of all types of lung cancer and is the leading cause of worldwide cancer-associated mortalities. MiR-124 is epigenetically silenced in various types of cancer and plays important roles in tumor development and progression. MiR-124 was also significantly downregulated in non–small cell lung cancer patients. Glycolysis has been considered as a feature of cancer cells; hypoxia-inducible factor 1-alpha/beta and Akt are key enzymes in the regulation of glycolysis and energy metabolism in cancer cells. However, the role of miR-124 in non–small cell lung cancer cell proliferation, glycolysis, and energy metabolism remains unknown. In this research, cell proliferation was investigated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; furthermore, glucose consumption and lactic acid production were assessed; adenosine triphosphate content and NAD+/NADH were also detected. These tests were conducted using the normal non–small cell lung cancer cell line A549, which was transfected variedly with miR-mimics, miR-124 mimics, miR-124 inhibitor, pc-DNA3.1(+)-AKT1, and pc-DNA3.1(+)-AKT2 plasmid. Here, we show that miR-124 overexpression directly decreased cell growth, glucose consumption, lactate production, and energy metabolism. MiR-124 also negatively regulates glycolysis rate–limiting enzymes, glucose transporter 1 and hexokinase II. Our results also showed that miR-124 negatively regulates AKT1 and AKT2 but no regulatory effect on hypoxia-inducible factor 1-alpha/beta. Overexpression of AKT reverses the inhibitory effect of miR-124 on cell proliferation and glycolytic metabolism in non–small cell lung cancer. AKT inhibition blocks miR-124 silencing–induced AKT1/2, glucose transporter 1, hexokinase II activation, cell proliferation, and glycolytic or energy metabolism changes. In summary, this study demonstrated that miR-124 is able to inhibit proliferation, glycolysis, and energy metabolism, potentially by targeting AKT1/2–glucose transporter 1/hexokinase II in non–small cell lung cancer cells.

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