Metal-based glycoconjugates and their potential in targeted anticancer chemotherapy

Metallodrugs ◽  
2016 ◽  
Vol 1 (1) ◽  
Author(s):  
Andrea Pettenuzzo ◽  
Rebecca Pigot ◽  
Luca Ronconi
Keyword(s):  
Cell Growth ◽  
Glucose Metabolism ◽  
Tumor Progression ◽  
Cancer Cells ◽  
Anticancer Agents ◽  
Glycolytic Flux ◽  
Cellular Internalization ◽  
Site Specific ◽  
Anticancer Chemotherapy ◽  
Essential Nutrient

AbstractGlucose is a key source of energy and an essential nutrient for cell growth. Rapidly dividing cancer cells are well-known to require more nutrients and energy than normal ones to sustain their higher proliferation rates, and glucose is no exception. Therefore, the biomolecules involved in the promotion/regulation of the glycolytic flux may be regarded as potential targets for tackling tumor progression. Among all, glucose transporters (GLUTs), devoted to the recognition and cellular internalization of glucose, are largely overexpressed in tumors, thus indicating glycolysis as the major anaerobic glucose metabolism. Accordingly, such increased demand of glucose by fast-proliferating cancer cells makes it very attractive to selectively target tumor sites. In particular, tailored glucose-like substrates can be conjugated to chemotherapeutics (including metal-containing anticancer agents) so as to attain the site-specific delivery of drugs into the affected tissues. Progress in the development of metal-based glycoconjugates are here summarized and discussed.

scholarly journals Glucose Metabolism in Pancreatic Cancer

Cancers ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 1460 ◽  
Author(s):  
Liang Yan ◽  
Priyank Raj ◽  
Wantong Yao ◽  
Haoqiang Ying
Keyword(s):  
Pancreatic Cancer ◽  
Glucose Metabolism ◽  
Cancer Cells ◽  
Redox Homeostasis ◽  
Central Carbon Metabolism ◽  
Ductal Adenocarcinoma ◽  
Glycolytic Flux ◽  
Pancreatic Cancer Cells ◽  
Cellular Energetics ◽  
Salvage Pathways

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and lethal cancers, with a five-year survival rate of around 5% to 8%. To date, very few available drugs have been successfully used to treat PDAC due to the poor understanding of the tumor-specific features. One of the hallmarks of pancreatic cancer cells is the deregulated cellular energetics characterized by the “Warburg effect”. It has been known for decades that cancer cells have a dramatically increased glycolytic flux even in the presence of oxygen and normal mitochondrial function. Glycolytic flux is the central carbon metabolism process in all cells, which not only produces adenosine triphosphate (ATP) but also provides biomass for anabolic processes that support cell proliferation. Expression levels of glucose transporters and rate-limiting enzymes regulate the rate of glycolytic flux. Intermediates that branch out from glycolysis are responsible for redox homeostasis, glycosylation, and biosynthesis. Beyond enhanced glycolytic flux, pancreatic cancer cells activate nutrient salvage pathways, which includes autophagy and micropinocytosis, from which the generated sugars, amino acids, and fatty acids are used to buffer the stresses induced by nutrient deprivation. Further, PDAC is characterized by extensive metabolic crosstalk between tumor cells and cells in the tumor microenvironment (TME). In this review, we will give an overview on recent progresses made in understanding glucose metabolism-related deregulations in PDAC.

scholarly journals Integrating transcriptomics and proteomics to show that tanshinone IIA suppresses cell growth by blocking glucose metabolism in gastric cancer cells

BMC Genomics ◽  
2015 ◽  
Vol 16 (1) ◽  
pp. 41 ◽  
Author(s):  
Li-Ling Lin ◽  
Chieh-Ren Hsia ◽  
Chia-Lang Hsu ◽  
Hsuan-Cheng Huang ◽  
Hsueh-Fen Juan
Keyword(s):  
Gastric Cancer ◽  
Cell Growth ◽  
Glucose Metabolism ◽  
Cancer Cells ◽  
Tanshinone Iia ◽  
Gastric Cancer Cells

scholarly journals Upregulation of glucose metabolism by NF-κB2/p52 mediates enzalutamide resistance in castration-resistant prostate cancer cells

2014 ◽  
Vol 21 (3) ◽  
pp. 435-442 ◽  
Author(s):  
Yuanyuan Cui ◽  
Nagalakshmi Nadiminty ◽  
Chengfei Liu ◽  
Wei Lou ◽  
Chad T Schwartz ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Growth ◽  
Glucose Metabolism ◽  
Cancer Cells ◽  
Culture Media ◽  
Lactate Production ◽  
Lncap Cells ◽  
Prostate Cancer Cells ◽  
Increase Glucose Uptake ◽  
Glucose Flux

Cancer cells reprogram their metabolic pathways to facilitate fast proliferation. Previous studies have shown that overexpression of NF-κB2/p52 (p52) in prostate cancer cells promotes cell growth and leads to castration resistance through aberrant activation of androgen receptor (AR). In addition, these cells become resistant to enzalutamide. In this study, we investigated the effects of p52 activation on glucose metabolism and on response to enzalutamide therapy. Data analysis of gene expression arrays showed that genes includingGLUT1(SLC2A1),PKM2,G6PD, andME1involved in the regulation of glucose metabolism were altered in LNCaP cells overexpressing p52 compared with the parental LNCaP cells. We demonstrated an increased amount of glucose flux in the glycolysis pathway, as well as the pentose phosphate pathway (PPP) upon p52 activation. The p52-overexpressing cells increase glucose uptake and are capable of higher ATP and lactate production compared with the parental LNCaP cells. The growth of p52-overexpressing cells depends on glucose in the culture media and is sensitive to glucose deprivation compared with the parental LNCaP cells. Targeting glucose metabolism by the glucose analog 2-deoxy-d-glucose synergistically inhibits cell growth when combined with enzalutamide, and resensitizes p52-overexpressing cells to enzalutamide treatment. These results suggest that p52 modulates glucose metabolism, enhances glucose flux to glycolysis and PPPs, thus facilitating fast proliferation of the cells. Co-targeting glucose metabolism together with AR axis synergistically inhibits cell growth and restores enzalutamide-resistant cells to enzalutamide treatment.

scholarly journals One-pot, multi-component synthesis of novel 2-amino-[1,2,4]triazolo[1,5-a] pyrimidine-6-carboxamide derivatives as antiproliferative agents 

2021 ◽  
Author(s):  
Xian-Sen Huo ◽  
Yu-Feng Ma ◽  
Zhi-Ru Chen ◽  
Li-Li Yuan ◽  
Xiao-Lan Zheng ◽  
...  
Keyword(s):  
Cell Growth ◽  
Cancer Cells ◽  
Anticancer Agents ◽  
Inhibition Activity ◽  
Cell Growth Inhibition ◽  
Cancer Cell Growth ◽  
One Pot ◽  
Antiproliferative Agents ◽  
Heterocyclization Reaction ◽  
Growth Inhibition Activity

Abstract A novel series of 2-amino-[1,2,4]triazolo[1,5-a]pyrimidine-6-carboxamide derivatives has been achieved successfully via an efficient one-pot three-component Biginelli-like heterocyclization reaction between different benzaldehydes, 1H-1,2,4-triazole-3,5-diamine, and N-substituted acetoacetamides in the presence of p-toluenesulfonic acid as a catalyst. Moreover, the effects of different conditions on the reaction were well investigated. In addition, cancer cell growth inhibition activity for these target compounds was also explored, and analogue 5l demonstrated the most potent cytotoxic activity against different cancer cells. These finds indicat that 2-amino-[1,2,4]triazolo[1,5-a]pyrimidine-6-carboxamide core could be well worth further optimization as a potential scaffold for development of anticancer agents.

scholarly journals Effect of MED28 on Glucose Transporters and Glycolysis in Human Colorectal Cancer Cells

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1248-1248
Author(s):  
Yu-Tsen Chang ◽  
Po-Chen Li ◽  
An-Chin Cheng ◽  
Ming-Fen Lee
Keyword(s):  
Colorectal Cancer ◽  
Cell Growth ◽  
Glucose Metabolism ◽  
Cancer Cells ◽  
Glucose Transporters ◽  
Human Colorectal Cancer ◽  
Colorectal Cancer Cells ◽  
Human Colorectal Cancer Cells ◽  
Hct116 Cells

Abstract Objectives MED28 exhibits several cellular roles, including a Mediator subunit for transcriptional activation as well as an interactor with merlin, NF2 tumor suppressor protein, and Grb2, a signaling adaptor. Our laboratory has previously reported that MED28 not only mediates cell growth but also appears to regulate glucose metabolism in human colorectal cancer cells. Therefore, the objective of the current study is to investigate the in vivo effect of MED28 on glucose metabolism and cell growth in colorectal cancer. Methods HCT116 colorectal cancer cells were transfected with MED28 siRNA or non-target siRNA for 72 h, and then undergone Western blotting or immunofluorescence analysis, by incubating with anti-c-Myc antibodies and DAPI for nuclear staining. We also established shMED28-transfected HCT116 cells and employed a NOD/SCID immunodeficient mouse xenograft model by subcutaneously implanting 1 × 107 stably transfected cells to the flanks of the animals to study the in vivo effect of MED28 expression on glucose metabolism. The animal study continued for 21 days, and the animal use protocol was approved by the Institutional Animal Care and Use Committee. The subcutaneous tumors were analyzed for the expression of MED28, glucose transporter 1 (GLUT1), and glycolysis-associated enzymes, including hexokinase 2 (HK2) and lactate dehydrogenase A (LDHA). Results The expression of c-Myc was decreased upon MED28 knockdown in HCT116 cells. Our in vivo data indicated smaller xenograft volumes and lower expression levels of MED28, GLUT1, HK2, and LDHA in tumors carrying shMED28-transfected HCT116 cells than those of control counterparts. Conclusions MED28 upregulates glucose transporters and glycolysis-associated enzymes as well as cell growth in NOD/SCID subcutaneous xenografts, suggesting nutrient-gene interactions between glucose metabolism and MED28 in human colorectal cancer cells. Funding Sources This work was supported by the grants MOST106–2320-B-039–062-MY3 and CMU108-SR-31 to M-F Lee, and MOST108–2813-C-039–058-B to Y-T Chang.

scholarly journals Shemamruthaa, a Herbal Formulation Induces Apoptosis in Breast Cancer Cells and Inhibits Tumor Progression in Rats

2016 ◽  
Vol 21 (4) ◽  
pp. NP1-NP10 ◽  
Author(s):  
Ayyakkannu Purushothaman ◽  
Elumalai Nandhakumar ◽  
Palanivelu Shanthi ◽  
Thiruvaiyaru Panchanatham Sachidanandam
Keyword(s):  
Breast Cancer ◽  
Tumor Progression ◽  
Cancer Cells ◽  
Anticancer Agents ◽  
High Performance ◽  
Therapeutic Potential ◽  
Gas Chromatography Mass Spectrometry ◽  
Dependent Manner ◽  
Chromatography Analysis ◽  
Herbal Formulation

Phytochemicals present in plants are more effective than their individual constituents in preventing cancer through synergetic effects. From this perspective, Shemamruthaa, a herbal formulation was evaluated with a view to potentiate more intense anticancer property. This study investigates the anticancer activity of Shemamruthaa in breast cancer (MDA-MB 231) cell lines and its cancer therapeutic potential in 7,12-dimethylbenz[a]anthracene induced breast cancer rats. Results of MTT, trypan blue, and apoptotic marker assays suggested that Shemamruthaa can induce cytotoxicity in cancer cells, in a concentration- and time-dependent manner. Oral administration of Shemamruthaa effectively suppressed the tumor progression as evidenced by decrease in tumor volume and modulation of oxidant-antioxidant status and resulted in extended life span. Gas chromatography–mass spectrometry and high-performance liquid chromatography analysis of Shemamruthaa revealed the presence of pyrogallol, 5-hydrxoymethylfurfural, trilinolein, and flavonoids. Finally, we show that Shemamruthaa contains potential anticancer agents acting either singly or in combination against breast cancer cell proliferation.

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