scholarly journals Metabolic Heterogeneity of Cancer Cells: An Interplay between Reprogrammed and Oxidative Metabolism and Roles of HIF-1, GLUTs and AMPK

2020 ◽  
Author(s):  
Nurbubu T. Moldogazieva ◽  
Innokenty M. Mokhosoev ◽  
Alexander A. Terentiev
Keyword(s):  
Cancer Cells ◽  
Cancer Cell ◽  
Oxidative Metabolism ◽  
Cell Metabolism ◽  
Hypoxia Inducible Factor ◽  
Metabolic Plasticity ◽  
Anti Cancer ◽  
Cancer Cell Metabolism ◽  
Metabolic Heterogeneity ◽  
Amp Activated Protein Kinase

It has been long recognized that under hypoxia conditions cancer cells reprogram their metabolism through shift from oxidative phosphorylation (OXPHOS) to glycolysis to meet elevated requirements in energy and nutrients for proliferation, migration and survival. However, data accumulated over the last years increasingly evidence that cancer cells can revert from glycolysis to OXPHOS and maintain both reprogrammed and oxidative metabolism even in the same tumor. The phenomenon denoted as cancer cell metabolic plasticity or hybrid metabolism depends on a tumor micro-environment, which is highly heterogeneous and influenced by intensity of vasculature and blood flow, oxygen concentration, nutrient and energy supply, and requires regulatory interplay between multiple oncogenes, transcription factors, growth factors, reactive oxygen species (ROS), etc. Hypoxia-inducible factor-1 (HIF-1) and AMP-activated protein kinase (AMPK) represent key modulators of switch between reprogrammed and oxidative metabolism. The present review focuses on cross-talks between HIF-1, GLUTs, and AMPK and other regulatory proteins including oncogenes such as c-Myc, p53 and KRAS, growth factor-initiated PKB/Akt, PI3K and mTOR signaling pathways and tumor suppressors such as LKB1 and TSC1 in controlling cancer cell metabolism. The multiple switches between metabolic pathways can underlie chemo-resistance to conventional anti-cancer therapy and should be taken into account in choosing molecular targets to discovery novel anti-cancer drugs.

scholarly journals Metabolic Heterogeneity of Cancer Cells: An Interplay between HIF-1, GLUTs, and AMPK

Cancers ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 862 ◽  
Author(s):  
Nurbubu T. Moldogazieva ◽  
Innokenty M. Mokhosoev ◽  
Alexander A. Terentiev
Keyword(s):  
Protein Kinase ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Oxidative Metabolism ◽  
Cell Metabolism ◽  
Hypoxia Inducible Factor ◽  
Anti Cancer ◽  
Liver Kinase B1 ◽  
Metabolic Heterogeneity ◽  
Amp Activated Protein Kinase

It has been long recognized that cancer cells reprogram their metabolism under hypoxia conditions due to a shift from oxidative phosphorylation (OXPHOS) to glycolysis in order to meet elevated requirements in energy and nutrients for proliferation, migration, and survival. However, data accumulated over recent years has increasingly provided evidence that cancer cells can revert from glycolysis to OXPHOS and maintain both reprogrammed and oxidative metabolism, even in the same tumor. This phenomenon, denoted as cancer cell metabolic plasticity or hybrid metabolism, depends on a tumor micro-environment that is highly heterogeneous and influenced by an intensity of vasculature and blood flow, oxygen concentration, and nutrient and energy supply, and requires regulatory interplay between multiple oncogenes, transcription factors, growth factors, and reactive oxygen species (ROS), among others. Hypoxia-inducible factor-1 (HIF-1) and AMP-activated protein kinase (AMPK) represent key modulators of a switch between reprogrammed and oxidative metabolism. The present review focuses on cross-talks between HIF-1, glucose transporters (GLUTs), and AMPK with other regulatory proteins including oncogenes such as c-Myc, p53, and KRAS; growth factor-initiated protein kinase B (PKB)/Akt, phosphatidyl-3-kinase (PI3K), and mTOR signaling pathways; and tumor suppressors such as liver kinase B1 (LKB1) and TSC1 in controlling cancer cell metabolism. The multiple switches between metabolic pathways can underlie chemo-resistance to conventional anti-cancer therapy and should be taken into account in choosing molecular targets to discover novel anti-cancer drugs.

scholarly journals A Holistic Evolutionary and 3D Pharmacophore Modelling Study Provides Insights into the Metabolism, Function, and Substrate Selectivity of the Human Monocarboxylate Transporter 4 (hMCT4)

2021 ◽  
Vol 22 (6) ◽  
pp. 2918
Author(s):  
Eleni Papakonstantinou ◽  
Dimitrios Vlachakis ◽  
Trias Thireou ◽  
Panayiotis G. Vlachoyiannopoulos ◽  
Elias Eliopoulos
Keyword(s):  
Cancer Cell ◽  
Structural Characteristics ◽  
Cell Metabolism ◽  
Intracellular Localization ◽  
Selective Inhibition ◽  
Monocarboxylate Transporter ◽  
Cancer Drug ◽  
Pharmacophore Modelling ◽  
Anti Cancer ◽  
Cancer Cell Metabolism

Monocarboxylate transporters (MCTs) are of great research interest for their role in cancer cell metabolism and their potential ability to transport pharmacologically relevant compounds across the membrane. Each member of the MCT family could potentially provide novel therapeutic approaches to various diseases. The major differences among MCTs are related to each of their specific metabolic roles, their relative substrate and inhibitor affinities, the regulation of their expression, their intracellular localization, and their tissue distribution. MCT4 is the main mediator for the efflux of L-lactate produced in the cell. Thus, MCT4 maintains the glycolytic phenotype of the cancer cell by supplying the molecular resources for tumor cell proliferation and promotes the acidification of the extracellular microenvironment from the co-transport of protons. A promising therapeutic strategy in anti-cancer drug design is the selective inhibition of MCT4 for the glycolytic suppression of solid tumors. A small number of studies indicate molecules for dual inhibition of MCT1 and MCT4; however, no selective inhibitor with high-affinity for MCT4 has been identified. In this study, we attempt to approach the structural characteristics of MCT4 through an in silico pipeline for molecular modelling and pharmacophore elucidation towards the identification of specific inhibitors as a novel anti-cancer strategy.

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 Targeting cancer cell metabolism with mitochondria-immobilized phosphorescent cyclometalated iridium(iii) complexes

2017 ◽  
Vol 8 (1) ◽  
pp. 631-640 ◽  
Author(s):  
Jian-Jun Cao ◽  
Cai-Ping Tan ◽  
Mu-He Chen ◽  
Na Wu ◽  
De-Yang Yao ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Cancer Cell ◽  
Rational Design ◽  
Cell Metabolism ◽  
Mitochondrial Metabolism ◽  
Cancer Cell Metabolism

We report a rational design and mechanism studies of mitochondria-immobilized iridium(iii) complexes that can kill cancer cells by targeting mitochondrial metabolism.

Targeting Cancer Cell Metabolism: The Combination of Metformin and 2-Deoxyglucose Induces p53-Dependent Apoptosis in Prostate Cancer Cells

2010 ◽  
Vol 70 (6) ◽  
pp. 2465-2475 ◽  
Author(s):  
Issam Ben Sahra ◽  
Kathiane Laurent ◽  
Sandy Giuliano ◽  
Frédéric Larbret ◽  
Gilles Ponzio ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Cell Metabolism ◽  
Prostate Cancer Cells ◽  
Cancer Cell Metabolism

Metabolic and amino acid alterations of the tumor microenvironment

2020 ◽  
Vol 27 ◽  
Author(s):  
Petr Stepka ◽  
Vit Vsiansky ◽  
Martina Raudenska ◽  
Jaromir Gumulec ◽  
Vojtech Adam ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Amino Acids ◽  
Amino Acid ◽  
Tumor Microenvironment ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Warburg Effect ◽  
Cell Metabolism ◽  
Metastatic Potential ◽  
Cancer Cell Metabolism

: Metabolic changes driven by the hostile tumor microenvironment surrounding cancer cells and effect of these changes on tumorigenesis and metastatic potential have been known for a long time. The usual point of interest is glucose and changes in its utilization by cancer cells, mainly in the form of the Warburg effect. However, amino acids, both intra- and extracellular, also represent an important aspect of tumour microenvironment, which can have a significant effect on cancer cell metabolism and overall development of the tumor. Namely alterations in metabolism of amino acids glutamine, sarcosine, aspartate, methionine and cysteine have been previously connected to the tumor progression and aggressivity of prostate cancer. The aim of this review is to pinpoint current gaps in our knowledge of the role of amino acids as a part of the tumor microenvironment and to show effect of various amino acids on cancer cell metabolism and metastatic potential. This review shows limitations and exceptions from the traditionally accepted model of Warburg effect in some cancer tissues, with the emphasis on prostate cancer, because the traditional definition of Warburg effect as a metabolic switch to aerobic glycolysis does not always apply. Prostatic tissue both in healthy and transformed state significantly differs in many metabolic aspects, including the metabolisms of glucose and amino acids, from metabolism of other tissues. Findings from different tissues are therefore not always interchangeable and have to be taken into account during experimentation modifying the environment of tumor tissue by amino acid supplementation or depletion, which could potentially serve as a new therapeutic approach.

Pieces of the complex puzzle of cancer cell energy metabolism: an overview of energy metabolism and alternatives for targeted cancer therapy

2020 ◽  
Vol 27 ◽  
Author(s):  
Zeinab Ghasemishahrestani ◽  
Larissa Maura Melo Mattos ◽  
Tatiana Martins Tilli ◽  
André Souza dos Santos ◽  
Marcos Dias Pereira
Keyword(s):  
Energy Metabolism ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Cancer Progression ◽  
Warburg Effect ◽  
Cell Biology ◽  
Aerobic Glycolysis ◽  
Target Therapy ◽  
Cell Metabolism ◽  
Cancer Cell Metabolism

Over the past decades, several advances in cancer cell biology have led to relevant details about a phenomenon called "Warburg effect". Currently, it has been accepted that Warburg effect is not anymore compatible with all cancer cells, and thus the process of aerobic glycolysis is now challenged by the knowledge of a large number of cells presenting mitochondrial function. The energy metabolism of cancer cells is focused in the bioenergetic and biosynthetic pathways to meet the requirements of rapid proliferation. Changes in the metabolism of carbohydrate, amino acids and lipids have already been reported in cancer cells and might play relevant roles for cancer progression. To the best of our knowledge, mostly of these changes are established, mainly due to genetic reprogramming that leads to the transformation of a healthy into a cancerous cell. Indeed, several enzymes of high relevance for the energy are targets of oncogenes (ex. PI3K, HIF1 and Myc) and tumor suppressor proteins (ex. p53). As a consequence of the extensive study on cancer cell metabolism, some new therapeutic strategies have appeared that aim to interrupt the aberrant metabolism, as well as the influence of genetic reprogramming in cancer cells. In this perspective, we briefly review the cancer cell metabolism (carbohydrate, amino acid and lipid), and also describe oncogenes and tumor suppressors that affect cancer cell metabolism. We also discuss some potential candidates for target therapy to disrupt the main driven-force for cancer cell metabolism and proliferation.

scholarly journals Mitochondrial VDAC1 Silencing Leads to Metabolic Rewiring and the Reprogramming of Tumour Cells into Advanced Differentiated States

Cancers ◽  
2018 ◽  
Vol 10 (12) ◽  
pp. 499 ◽  
Author(s):  
Tasleem Arif ◽  
Avijit Paul ◽  
Yakov Krelin ◽  
Anna Shteinfer-Kuzmine ◽  
Varda Shoshan-Barmatz
Keyword(s):  
Lung Cancer ◽  
Cell Differentiation ◽  
Cell Growth ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Tumour Growth ◽  
Cell Metabolism ◽  
Metabolic Reprogramming ◽  
Residual Tumour ◽  
Cancer Cell Metabolism

Oncogenic properties, along with the metabolic reprogramming necessary for tumour growth and motility, are acquired by cancer cells. Thus, tumour metabolism is becoming a target for cancer therapy. Here, cancer cell metabolism was tackled by silencing the expression of voltage-dependent anion channel 1 (VDAC1), a mitochondrial protein that controls cell energy, as well as metabolic and survival pathways and that is often over-expressed in many cancers. We demonstrated that silencing VDAC1 expression using human-specific siRNA (si-hVDAC1) inhibited cancer cell growth, both in vitro and in mouse xenograft models of human glioblastoma (U-87MG), lung cancer (A549), and triple negative breast cancer (MDA-MB-231). Importantly, treatment with si-hVDAC1 induced metabolic rewiring of the cancer cells, reversing their oncogenic properties and diverting them towards differentiated-like cells. The si-hVDAC1-treated residual “tumour” showed reprogrammed metabolism, decreased proliferation, inhibited stemness and altered expression of genes and proteins, leading to cell differentiation toward less malignant lineages. These VDAC1 depletion-mediated effects involved alterations in master transcription factors associated with cancer hallmarks, such as highly increased expression of p53 and decreased expression of HIF-1a and c-Myc that regulate signalling pathways (e.g., AMPK, mTOR). High expression of p53 and the pro-apoptotic proteins cytochrome c and caspases without induction of apoptosis points to functions for these proteins in promoting cell differentiation. These results clearly show that VDAC1 depletion similarly leads to a rewiring of cancer cell metabolism in breast and lung cancer and glioblastoma, regardless of origin or mutational status. This metabolic reprogramming results in cell growth arrest and inhibited tumour growth while encouraging cell differentiation, thus generating cells with decreased proliferation capacity. These results further suggest VDAC1 to be an innovative and markedly potent therapeutic target.

scholarly journals Anti-cancer agents and reactive oxygen species modulators that target cancer cell metabolism

2017 ◽  
Vol 89 (9) ◽  
pp. 1333-1348
Author(s):  
Fidelis Toloyi Ndombera
Keyword(s):  
Reactive Oxygen Species ◽  
Cancer Cells ◽  
Cell Metabolism ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Functional Studies ◽  
Anti Cancer ◽  
Cancer Cell Metabolism ◽  
Protective Threshold ◽  
Target Cancer

AbstractTraditionally the perspective on reactive oxygen species (ROS) has centered on the role they play as carcinogenic or cancer-causing radicals. Over the years, characterization and functional studies have revealed the complexity of ROS as signaling molecules that regulate various physiological cellular responses or whose levels are altered in various diseases. Cancer cells often maintain high basal level of ROS and are vulnerable to any further increase in ROS levels beyond a certain protective threshold. Consequently, ROS-modulation has emerged as an anticancer strategy with synthesis of various ROS-inducing or responsive agents that target cancer cells. Of note, an increased carbohydrate uptake and/or induction of death receptors of cancer cells was exploited to develop glycoconjugates that potentially induce cellular stress, ROS and apoptosis. This mini review highlights the development of compounds that target cancer cells by taking advantage of redox or metabolic alteration in cancer cells.

Sign in / Sign up

Export Citation Format

Share Document