Lactate Formation in Primary and Metastatic Colon Cancer Cells at Hypoxia and Normoxia

Graboń, Wojciech; Otto-Ślusarczyk, Dagmara; Chrzanowska, Alicja; Mielczarek-Puta, Magdalena; Joniec-Maciejak, Ilona; Słabik, Krzysztof; Barańczyk‐Kuźma, Anna

doi:10.1002/cbf.3211

Cited by 16 publications

(11 citation statements)

References 30 publications

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“…The literature showed butyrate is absorbed by rectal colon cells in special by the monocarboxylate transporters (MCT)-1 [44]. The butyrate absorption could be inhibited in tumour colonic cells, whereas MCTs are associated with the efflux and influx of lactate, which is increased in colon cancer cells [45]. Moreover, patients with intestinal bowel diseases display downregulation of bile acid uptake transporter [46], increased intestinal permeability, and disruption of intestinal barrier [47], demonstrating that bowel inflammation can alter digestion and nutrients uptake.…”

Section: Discussionmentioning

confidence: 99%

Tributyrin in Inflammation: Does White Adipose Tissue Affect Colorectal Cancer?

et al. 2019

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Colorectal cancer affects the large intestine, leading to loss of white adipose tissue (WAT) and alterations in adipokine secretion. Lower incidence of colorectal cancer is associated with increased fibre intake. Fructooligosaccharides (FOS) are fibres that increase production of butyrate by the intestinal microbiota. Tributyrin, a prodrug of butyric acid, exerts beneficial anti-inflammatory effects on colorectal cancer. Our aim was to characterise the effects of diets rich in FOS and tributyrin within the context of a colon carcinogenesis model, and characterise possible support of tumorigenesis by WAT. C57/BL6 male mice were divided into four groups: a control group (CT) fed with chow diet and three colon carcinogenesis-induced groups fed either with chow diet (CA), tributyrin-supplemented diet (BUT), or with FOS-supplemented diet. Colon carcinogenesis decreased adipose mass in subcutaneous, epididymal, and retroperitoneal tissues, while also reducing serum glucose and leptin concentrations. However, it did not alter the concentrations of adiponectin, interleukin (IL)-6, IL-10, and tumour necrosis factor alpha (TNF)-α in WAT. Additionally, the supplements did not revert the colon cancer affected parameters. The BUT group exhibited even higher glucose tolerance and levels of IL-6, VEGF, and TNF-α in WAT. To conclude our study, FOS and butyrate supplements were not beneficial. In addition, butyrate worsened adipose tissue inflammation.

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Section: Discussionmentioning

confidence: 99%

Tributyrin in Inflammation: Does White Adipose Tissue Affect Colorectal Cancer?

et al. 2019

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“…As a further contrast, a comparison of tumor tissue with non-tumor esophageal tissue failed to identify the increase in glycolytic intermediates [156] that would be anticipated by the scenario in Figure 3. Although it is generally thought that most lactate is derived from glycolysis [109,157,158], Figure 3 also does not consider that lactate can be derived from the metabolism of glutamine or serine [158][159][160][161][162][163][164]. Therefore, although Figure 3 offers an explanation that circumvents the apparent paradox introduced by M 2 PYK "inhibition" vs. increased lactic acid production, the entire assumption of the M 2 PYK inhibition is what should be questioned.…”

Section: Introductionmentioning

confidence: 99%

A critical review of the role of M2PYK in the Warburg effect

Harris

Fenton

2019

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

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It is becoming generally accepted in recent literature that the Warburg effect in cancer depends on inhibition of M 2 PYK, the pyruvate kinase isozyme most commonly expressed in tumors. We remain skeptical. There continues to be a general lack of solid experimental evidence for the underlying idea that a bottle neck in aerobic glycolysis at the level of M 2 PYK results in an expanded pool of glycolytic intermediates (which are thought to serve as building blocks necessary for proliferation and growth of cancer cells). If a bottle neck at M 2 PYK exists, then the remarkable increase in lactate production by cancer cells is a paradox, particularly since a high percentage of the carbons of lactate originate from glucose. The finding that pyruvate kinase activity is invariantly increased rather than decreased in cancer undermines the logic of the M 2 PYK bottle neck, but is consistent with high lactate production. The "inactive" state of M 2 PYK in cancer is often described as a dimer (with reduced substrate affinity) that has dissociated from an active tetramer of M 2 PYK. Although M 2 PYK clearly dissociates easier than other isozymes of pyruvate kinase, it is not clear that dissociation of the tetramer occurs in vivo when ligands are present that promote tetramer formation. Furthermore, it is also not clear whether the dissociated dimer retains any activity at all. A number of non-canonical functions for M 2 PYK have been proposed, all of which can be challenged by the finding that not all cancer cell types are dependent on M 2 PYK expression. Additional in-depth studies of the Warburg effect and specifically of the possible regulatory role of M 2 PYK in the Warburg effect are needed.

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“…Interestingly, oxygen deficit is not necessarily a determinant of reduced cancer cell proliferation. During hypoxia, the concentration of building and energy compounds in the tumour environment decreases [53]. Thus, it can be concluded that low oxygen concentration is a signal for the adaptation of cellular metabolism to the simultaneous deficiency of energy and building blocks compounds.…”

Section: The Metabolic Heterogeneity Of Cancer Is Due To the Difficult Conditions 61 Effect Of Hypoxia On Metabolismmentioning

confidence: 99%

More Than Meets the Eye Regarding Cancer Metabolism

Kubicka

Matczak

Łabieniec-Watała

2021

IJMS

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In spite of the continuous improvement in our knowledge of the nature of cancer, the causes of its formation and the development of new treatment methods, our knowledge is still incomplete. A key issue is the difference in metabolism between normal and cancer cells. The features that distinguish cancer cells from normal cells are the increased proliferation and abnormal differentiation and maturation of these cells, which are due to regulatory changes in the emerging tumour. Normal cells use oxidative phosphorylation (OXPHOS) in the mitochondrion as a major source of energy during division. During OXPHOS, there are 36 ATP molecules produced from one molecule of glucose, in contrast to glycolysis which provides an ATP supply of only two molecules. Although aerobic glucose metabolism is more efficient, metabolism based on intensive glycolysis provides intermediate metabolites necessary for the synthesis of nucleic acids, proteins and lipids, which are in constant high demand due to the intense cell division in cancer. This is the main reason why the cancer cell does not “give up” on glycolysis despite the high demand for energy in the form of ATP. One of the evolving trends in the development of anti-cancer therapies is to exploit differences in the metabolism of normal cells and cancer cells. Currently constructed therapies, based on cell metabolism, focus on the attempt to reprogram the metabolic pathways of the cell in such a manner that it becomes possible to stop unrestrained proliferation.

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Lactate Formation in Primary and Metastatic Colon Cancer Cells at Hypoxia and Normoxia

Cited by 16 publications

References 30 publications

Tributyrin in Inflammation: Does White Adipose Tissue Affect Colorectal Cancer?

Tributyrin in Inflammation: Does White Adipose Tissue Affect Colorectal Cancer?

A critical review of the role of M2PYK in the Warburg effect

More Than Meets the Eye Regarding Cancer Metabolism

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