scholarly journals Keap1/Nrf2 pathway in the frontiers of cancer and non-cancer cell metabolism

2015 ◽  
Vol 43 (4) ◽  
pp. 639-644 ◽  
Author(s):  
Dionysios V. Chartoumpekis ◽  
Nobunao Wakabayashi ◽  
Thomas W. Kensler
Keyword(s):  
Cancer Cells ◽  
Cancer Cell ◽  
Metabolic Pathways ◽  
De Novo ◽  
Cell Metabolism ◽  
Acid Synthesis ◽  
Pentose Phosphate ◽  
De Novo Lipogenesis ◽  
Nrf2 Pathway ◽  
Cancer Cell Survival

Cancer cells adapt their metabolism to their increased needs for energy and substrates for protein, lipid and nucleic acid synthesis. Nuclear erythroid factor 2-like 2 (Nrf2) pathway is usually activated in cancers and has been suggested to promote cancer cell survival mainly by inducing a large battery of cytoprotective genes. This mini review focuses on metabolic pathways, beyond cytoprotection, which can be directly or indirectly regulated by Nrf2 in cancer cells to affect their survival. The pentose phosphate pathway (PPP) is enhanced by Nrf2 in cancers and aids their growth. PPP has also been found to be up-regulated in non-cancer tissues and other pathways, such as de novo lipogenesis, have been found to be repressed after activation of the Nrf2 pathway. The importance of these Nrf2-regulated metabolic pathways in cancer compared with non-cancer state remains to be determined. Last but not least, the importance of context about Nrf2 and cancer is highlighted as the Nrf2 pathway may be activated in cancers but its pharmacological activators are useful in chemoprevention.

scholarly journals Phytochemicals Block Glucose Utilization and Lipid Synthesis to Counteract Metabolic Reprogramming in Cancer Cells

2021 ◽  
Vol 11 (3) ◽  
pp. 1259
Author(s):  
Qiong Wu ◽  
Bo Zhao ◽  
Guangchao Sui ◽  
Jinming Shi
Keyword(s):  
Cancer Cells ◽  
Metabolic Pathways ◽  
De Novo ◽  
Aerobic Glycolysis ◽  
Structural Characteristics ◽  
Natural Compounds ◽  
Metabolic Reprogramming ◽  
De Novo Lipogenesis ◽  
Anticancer Activities ◽  
Substrate Analogs

Aberrant metabolism is one of the hallmarks of cancers. The contributions of dysregulated metabolism to cancer development, such as tumor cell survival, metastasis and drug resistance, have been extensively characterized. “Reprogrammed” metabolic pathways in cancer cells are mainly represented by excessive glucose consumption and hyperactive de novo lipogenesis. Natural compounds with anticancer activities are constantly being demonstrated to target metabolic processes, such as glucose transport, aerobic glycolysis, fatty acid synthesis and desaturation. However, their molecular targets and underlying anticancer mechanisms remain largely unclear or controversial. Mounting evidence indicated that these natural compounds could modulate the expression of key regulatory enzymes in various metabolic pathways at transcriptional and translational levels. Meanwhile, natural compounds could also inhibit the activities of these enzymes by acting as substrate analogs or altering their protein conformations. The actions of natural compounds in the crosstalk between metabolism modulation and cancer cell destiny have become increasingly attractive. In this review, we summarize the activities of natural small molecules in inhibiting key enzymes of metabolic pathways. We illustrate the structural characteristics of these compounds at the molecular level as either inhibitor of various enzymes or regulators of metabolic pathways in cancer cells. Our ultimate goal is to both facilitate the clinical application of natural compounds in cancer therapies and promote the development of novel anticancer therapeutics.

scholarly journals Untargeted Metabolomics Identifies Key Metabolic Pathways Altered by Thymoquinone in Leukemic Cancer Cells

Nutrients ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1792 ◽  
Author(s):  
Asma Ahmed AlGhamdi ◽  
Mohammed Razeeth Shait Mohammed ◽  
Mazin A. Zamzami ◽  
Abdulrahman L. Al-Malki ◽  
Mohamad Hasan Qari ◽  
...  
Keyword(s):  
Cell Survival ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Metabolic Pathways ◽  
Nigella Sativa ◽  
Experimental Studies ◽  
Nucleotide Metabolism ◽  
Untargeted Metabolomics ◽  
Sphingolipid Metabolism ◽  
Cancer Cell Survival

Thymoquinone (TQ), a naturally occurring anticancer compound extracted from Nigella sativa oil, has been extensively reported to possess potent anti-cancer properties. Experimental studies showed the anti-proliferative, pro-apoptotic, and anti-metastatic effects of TQ on different cancer cells. One of the possible mechanisms underlying these effects includes alteration in key metabolic pathways that are critical for cancer cell survival. However, an extensive landscape of the metabolites altered by TQ in cancer cells remains elusive. Here, we performed an untargeted metabolomics study using leukemic cancer cell lines during treatment with TQ and found alteration in approximately 335 metabolites. Pathway analysis showed alteration in key metabolic pathways like TCA cycle, amino acid metabolism, sphingolipid metabolism and nucleotide metabolism, which are critical for leukemic cell survival and death. We found a dramatic increase in metabolites like thymine glycol in TQ-treated cancer cells, a metabolite known to induce DNA damage and apoptosis. Similarly, we observed a sharp decline in cellular guanine levels, important for leukemic cancer cell survival. Overall, we provided an extensive metabolic landscape of leukemic cancer cells and identified the key metabolites and pathways altered, which could be critical and responsible for the anti-proliferative function of TQ.

AMPA Receptor Antagonist CFM-2 Decreases Survivin Expression in Cancer Cells

2018 ◽  
Vol 18 (4) ◽  
pp. 591-596 ◽  
Author(s):  
Domingo Sanchez Ruiz ◽  
Hella Luksch ◽  
Marco Sifringer ◽  
Achim Temme ◽  
Christian Staufner ◽  
...  
Keyword(s):  
Cell Survival ◽  
Receptor Antagonist ◽  
Cancer Cells ◽  
Glutamate Receptors ◽  
Cancer Cell ◽  
Ampa Receptor ◽  
Ampa Receptors ◽  
Survivin Expression ◽  
Ampa Receptor Antagonist ◽  
Cancer Cell Survival

Background: Glutamate receptors are widely expressed in different types of cancer cells. α-Amino-3- hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors are ionotropic glutamate receptors which are coupled to intracellular signaling pathways that influence cancer cell survival, proliferation, and migration. Blockade of AMPA receptors by pharmacologic compounds may potentially constitute an effective tool in anticancer treatment strategies. Method: Here we investigated the impact of the AMPA receptor antagonist CFM-2 on the expression of the protein survivin, which is known to promote cancer cell survival and proliferation. We show that CFM-2 inhibits survivin expression at mRNA and protein levels and decreases the viability of cancer cells. Using a stably transfected cell line which overexpresses survivin, we demonstrate that over-expression of survivin enhances cancer cell viability and attenuates CFM-2–mediated inhibition of cancer cell growth. Result: These findings point towards suppression of survivin expression as a new mechanism contributing to anticancer effects of AMPA antagonists.

scholarly journals Osteoblast-Derived Paracrine and Juxtacrine Signals Protect Disseminated Breast Cancer Cells from Stress

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1366
Author(s):  
Russell Hughes ◽  
Xinyue Chen ◽  
Natasha Cowley ◽  
Penelope D. Ottewell ◽  
Rhoda J. Hawkins ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Survival ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Breast Cancer Cells ◽  
Metastatic Breast ◽  
Accessory Cell ◽  
Cancer Cell Survival

Metastatic breast cancer in bone is incurable and there is an urgent need to develop new therapeutic approaches to improve survival. Key to this is understanding the mechanisms governing cancer cell survival and growth in bone, which involves interplay between malignant and accessory cell types. Here, we performed a cellular and molecular comparison of the bone microenvironment in mouse models representing either metastatic indolence or growth, to identify mechanisms regulating cancer cell survival and fate. In vivo, we show that regardless of their fate, breast cancer cells in bone occupy niches rich in osteoblastic cells. As the number of osteoblasts in bone declines, so does the ability to sustain large numbers of breast cancer cells and support metastatic outgrowth. In vitro, osteoblasts protected breast cancer cells from death induced by cell stress and signaling via gap junctions was found to provide important juxtacrine protective mechanisms between osteoblasts and both MDA-MB-231 (TNBC) and MCF7 (ER+) breast cancer cells. Combined with mathematical modelling, these findings indicate that the fate of DTCs is not controlled through the association with specific vessel subtypes. Instead, numbers of osteoblasts dictate availability of protective niches which breast cancer cells can colonize prior to stimulation of metastatic outgrowth.

scholarly journals Mitochondrial Transfer in Cancer: A Comprehensive Review

2021 ◽  
Vol 22 (6) ◽  
pp. 3245
Author(s):  
Luca X. Zampieri ◽  
Catarina Silva-Almeida ◽  
Justin D. Rondeau ◽  
Pierre Sonveaux
Keyword(s):  
Cancer Cells ◽  
Cancer Cell ◽  
Metabolic Pathways ◽  
Current Knowledge ◽  
Cancer Cell Proliferation ◽  
Tunneling Nanotubes ◽  
Comprehensive Review ◽  
Cancer Cell Death ◽  
Mitochondrial Transfer ◽  
Metabolic Activities

Depending on their tissue of origin, genetic and epigenetic marks and microenvironmental influences, cancer cells cover a broad range of metabolic activities that fluctuate over time and space. At the core of most metabolic pathways, mitochondria are essential organelles that participate in energy and biomass production, act as metabolic sensors, control cancer cell death, and initiate signaling pathways related to cancer cell migration, invasion, metastasis and resistance to treatments. While some mitochondrial modifications provide aggressive advantages to cancer cells, others are detrimental. This comprehensive review summarizes the current knowledge about mitochondrial transfers that can occur between cancer and nonmalignant cells. Among different mechanisms comprising gap junctions and cell-cell fusion, tunneling nanotubes are increasingly recognized as a main intercellular platform for unidirectional and bidirectional mitochondrial exchanges. Understanding their structure and functionality is an important task expected to generate new anticancer approaches aimed at interfering with gains of functions (e.g., cancer cell proliferation, migration, invasion, metastasis and chemoresistance) or damaged mitochondria elimination associated with mitochondrial transfer.

Effect of carbohydrate intake on de novo lipogenesis in human adipose tissue

1987 ◽  
Vol 253 (6) ◽  
pp. E664-E669 ◽  
Author(s):  
C. Chascione ◽  
D. H. Elwyn ◽  
M. Davila ◽  
K. M. Gil ◽  
J. Askanazi ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
De Novo ◽  
Acid Synthesis ◽  
De Novo Lipogenesis ◽  
Whole Body ◽  
High Intake ◽  
Carbohydrate Diet ◽  
Triglyceride Synthesis ◽  
High Carbohydrate

Rates of synthesis, from [14C]glucose, of fatty acids (de novo lipogenesis) and glycerol (triglyceride synthesis) were measured in biopsies of adipose tissue from nutritionally depleted patients given low- or high-carbohydrate intravenous nutrition. Simultaneously, energy expenditure and whole-body lipogenesis were measured by indirect calorimetry. Rates of whole-body lipogenesis were zero on the low-carbohydrate diet and averaged 1.6 g.kg-1.day-1 on the high-carbohydrate diet. In vitro rates of triglyceride synthesis increased 3-fold going from the low to the high intake; rates of fatty acid synthesis increased approximately 80-fold. In vitro, lipogenesis accounted for less than 0.1% of triglyceride synthesis on the low intake and 4% on the high intake. On the high-carbohydrate intake, in vitro rates of triglyceride synthesis accounted for 61% of the rates of unidirectional triglyceride synthesis measured by indirect calorimetry. In vitro rates of lipogenesis accounted for 7% of whole-body lipogenesis. Discrepancies between in vitro rates of fatty acid synthesis from glucose, compared with acetate and citrate, as reported by others, suggest that in depleted patients on hypercaloric high-carbohydrate diets, adipose tissue may account for up to 40% of whole-body lipogenesis.

Apoptosis triggered by isoquercitrin in bladder cancer cells by activating the AMPK-activated protein kinase pathway

2017 ◽  
Vol 8 (10) ◽  
pp. 3707-3722 ◽  
Author(s):  
Ping Wu ◽  
Siyuan Liu ◽  
Jianyu Su ◽  
Jianping Chen ◽  
Lin Li ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Protein Kinase ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Cell Metabolism ◽  
Bladder Cancer Cell ◽  
Bladder Cancer Cells ◽  
Immunoblotting Assay ◽  
Cancer Cell Metabolism ◽  
Kinase Pathway

Our findings provide comprehensive evidence that isoquercitrin (ISO) influenced T24 bladder cancer cell metabolism by activating the AMPK pathway as identified by combination with metabolomics and immunoblotting assay.

scholarly journals [Corrigendum] A combination of inhibitors of glycolysis, glutaminolysis and de�novo fatty acid synthesis decrease the expression of chemokines in human colon cancer cells

2020 ◽  
Author(s):  
Alejandro Schcolnik‑Cabrera ◽  
Guadalupe Dominguez‑G�mez ◽  
Alma Ch�vez‑Blanco ◽  
Marisol Ram�rez‑Yautentzi ◽  
Roc�o Morales‑B�rcenas ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Fatty Acid ◽  
Cancer Cells ◽  
Fatty Acid Synthesis ◽  
De Novo ◽  
Human Colon ◽  
Acid Synthesis ◽  
Colon Cancer Cells ◽  
Human Colon Cancer ◽  
Human Colon Cancer Cells

scholarly journals KSHV Reprogramming of Host Energy Metabolism for Pathogenesis

2021 ◽  
Vol 11 ◽  
Author(s):  
Xiaoqing Liu ◽  
Caixia Zhu ◽  
Yuyan Wang ◽  
Fang Wei ◽  
Qiliang Cai
Keyword(s):  
Energy Metabolism ◽  
Metabolic Pathways ◽  
B Lymphocyte ◽  
Aerobic Glycolysis ◽  
Cell Metabolism ◽  
Acid Synthesis ◽  
Central Carbon Metabolism ◽  
Central Carbon ◽  
Cell Energy ◽  
Infected Cells

Reprogramming of energy metabolism is a key for cancer development. Kaposi’s sarcoma-associated herpesvirus (KSHV), a human oncogenic herpesvirus, is tightly associated with several human malignancies by infecting B-lymphocyte or endothelial cells. Cancer cell energy metabolism is mainly dominated by three pathways of central carbon metabolism, including aerobic glycolysis, glutaminolysis, and fatty acid synthesis. Increasing evidence has shown that KSHV infection can alter central carbon metabolic pathways to produce biomass for viral replication, as well as the survival and proliferation of infected cells. In this review, we summarize recent studies exploring how KSHV manipulates host cell metabolism to promote viral pathogenesis, which provides the potential therapeutic targets and strategies for KSHV-associated cancers.

scholarly journals Palbociclib and fulvestrant act in synergy to modulate central carbon metabolism in breast cancer cells

2018 ◽  
Author(s):  
Benedikt Warth ◽  
Amelia Palermo ◽  
Nicholas J.W. Rattray ◽  
Nathan V Lee ◽  
Zhou Zhu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Cancer Cells ◽  
Pentose Phosphate Pathway ◽  
Metabolic Pathways ◽  
Breast Cancer Cells ◽  
Pentose Phosphate ◽  
List Type ◽  
Estrogen Receptor Positive ◽  
Positive Breast Cancer

SummaryPalbociclib, is a selective inhibitor of cyclin-dependent kinases 4 and 6 and used as a first-line treatment for patients with estrogen receptor positive breast cancer. It has been shown that patients have improved progression-free survival when treated in combination with fulvestrant, an estrogen receptor antagonist. However, the mechanisms for this survival advantage are not known. We sought to analyze metabolic and transcriptomic changes in MCF-7 adenocarcinoma breast cancer cells following single and combined treatments to determine if selective metabolic pathways are targeted during combination therapy. Our results showed that individually, the drugs caused metabolic disruption to the same metabolic pathways, however fulvestrant additionally attenuated the pentose phosphate pathway and the production of important coenzymes. A comprehensive effect was observed when the drugs were applied together, confirming the combinatory therapy′s synergism in the cell model. This study highlights the power of merging high-dimensional datasets to unravel mechanisms involved in cancer metabolism and therapy.Highlights○First study employing multi-omics to investigate combined therapy on breast cancer cells○Fulvestrant attenuates the pentose phosphate pathway and coenzyme production○Synergism of palbociclib and fulvestrant was confirmed in vitro○Altered key pathways have been identifiedeTOC BlurbJohnson et al. applied an innovative multi-omics approach to decipher metabolic pathways affected by single versus combination dosing of palbociclib and fulvestrant in estrogen receptor positive breast cancer. Key metabolites and genes were correlated within metabolic pathways and shown to be involved in the drugs′ synergism.

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