Krebs cycle: activators, inhibitors and their roles in the modulation of carcinogenesis

Gasmi, Amin; Peana, Massimiliano; Arshad, Maria; Butnariu, Monica; Menzel, Alain; Bjørklund, Geir

doi:10.1007/s00204-021-02974-9

Review Article
Published: 02 March 2021

Krebs cycle: activators, inhibitors and their roles in the modulation of carcinogenesis

Archives of Toxicology volume 95, pages 1161–1178 (2021)Cite this article

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Abstract

A fundamental metabolic feature of cancerous tissues is high glucose consumption. The rate of glucose consumption in a cancer cell can be 10–15 times higher than in normal cells. Isolation and cultivation of tumor cells in vitro highlight properties that are associated with intensive glucose utilization, the presence of minimal oxidative metabolism, an increase in lactate concentrations in the culture medium and a reduced rate of oxygen consumption. Although glycolysis is suggested as a general feature of malignant cells and recently identified as a possible contributing factor to tumor progression, several studies highlight distinct metabolic characteristics in some tumors, including a relative decrease in avidity compared to glucose and/or a glutamine dependency of lactate and even proliferative tumor cells. The aim of this review is to determine the particularities in the energy metabolism of cancer cells, focusing on the main nutritional substrates, such as glucose and glutamine, evaluating lactate dehydrogenase as a potential marker of malignancy and estimating activators and inhibitors in cancer treatment.

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Abbreviations

ACC:: Acetyl-CoA carboxylase
ACO2:: Aconitase
αKG:: α-Ketoglutarate
α-KGDH :: α-Ketoglutarate dehydrogenase
ATP:: Adenosine triphosphate
CPT1:: Carnitine palmitoyltransferase 1
CiC:: Mitochondrial citrate carrier
CoA:: Acetyl coenzyme A
COX:: Cytochrome c oxidase
DC:: Dendritic cell
FADH2:: Flavin adenine dinucleotide reduced form
HIF-1α:: Inducible factor of hypoxia alpha
GSH:: Glutathione
GTP:: Guanosine triphosphate
LDH:: Lactate dehydrogenase
NADH:: Nicotinamide adenine dinucleotide
NO:: Nitric oxide
Nrf2:: NNuclear factor erythroid 2-related factor 2
ROS:: Reactive oxygen species
TCA:: Tricarboxylic acid
TCAI:: Tricarboxylic acid intermediate

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Société Francophone de Nutrithérapie et de Nutrigénétique Appliquée, Villeurbanne, France
Amin Gasmi & Maria Arshad
Department of Chemistry and Pharmacy, University of Sassari, Sassari, Italy
Massimiliano Peana
Banat’s University of Agricultural Sciences and Veterinary Medicine “King Michael I of Romania” From Timisoara, Timisoara, Romania
Monica Butnariu
CONEM Romania Biotechnology and Environmental Sciences Group, Banat’s University of Agricultural Sciences and Veterinary Medicine “King Michael I of Romania” From Timisoara, Timisoara, Romania
Monica Butnariu
Laboratoires Réunis, Junglinster, Luxemburg
Alain Menzel
Council for Nutritional and Environmental Medicine (CONEM), Toften 24, 8610, Mo i Rana, Norway
Geir Bjørklund

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Gasmi, A., Peana, M., Arshad, M. et al. Krebs cycle: activators, inhibitors and their roles in the modulation of carcinogenesis. Arch Toxicol 95, 1161–1178 (2021). https://doi.org/10.1007/s00204-021-02974-9

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Received: 01 November 2020
Accepted: 04 January 2021
Published: 02 March 2021
Issue Date: April 2021
DOI: https://doi.org/10.1007/s00204-021-02974-9

Keywords

Krebs cycle
Cancer
Glucose
Glycolysis
Activators
Inhibitors