Glucose Metabolism in Cancer and Ischemia: Possible Therapeutic Consequences of the Warburg Effect

Šalamon, Špela; Podbregar, Eva; Kubatka, Peter; Büsselberg, Dietrich; Čaprnda, Martin; Opatřilová, Radka; Valentová, Vanda; Adamek, Mariusz; Kružliak, Peter; Podbregar, Matej

doi:10.1080/01635581.2017.1263751

Cited by 16 publications

(12 citation statements)

References 52 publications

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“…Previous studies have shown that there are obvious cellular metabolic disorders after ischemia induced by cancer or brain damage 34 . Therefore, we quantitatively analysed 400 metabolic markers and found that a series of metabolic molecules in vascular tissue varied significantly after ischemic injury (Fig.…”

Section: Drp1 Participates In Cellular Metabolic Disorders After Ischmentioning

confidence: 99%

Drp1 regulates mitochondrial dysfunction and dysregulated metabolism in ischemic injury via Clec16a-, BAX-, and GSH- pathways

et al. 2020

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The adaptation of mitochondrial homeostasis to ischemic injury is not fully understood. Here, we studied the role of dynamin-related protein 1 (Drp1) in this process. We found that mitochondrial morphology was altered in the early stage of ischemic injury while mitochondrial dysfunction occurred in the late stage of ischemia. Drp1 appeared to inhibit mitophagy by upregulating mito-Clec16a, which suppressed mito-Parkin recruitment and subsequently impaired the formation of autophagosomes in vascular tissues after ischemic injury. Moreover, ischemia-induced Drp1 activation enhanced apoptosis through inducing mitochondrial translocation of BAX and thereby increasing release of Cytochrome C to activate caspase-3/-9 signalling. Furthermore, Drp1 mediated metabolic disorders and inhibited the levels of mitochondrial glutathione to impair free radical scavenging, leading to further increases in ROS and the exacerbation of mitochondrial dysfunction after ischemic injury. Together, our data suggest a critical role for Drp1 in ischemic injury.

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Section: Drp1 Participates In Cellular Metabolic Disorders After Ischmentioning

confidence: 99%

Drp1 regulates mitochondrial dysfunction and dysregulated metabolism in ischemic injury via Clec16a-, BAX-, and GSH- pathways

et al. 2020

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“…Glucose is the primary source of energy in cancer cells (Salamon et al, 2017). Ketone bodies are the alternative fuels that could be used as a source of energy during starvation or strenuous exercises.…”

Section: Resultsmentioning

confidence: 99%

“…For years, we know that cancer cells convert glucose to lactate in the presence or absence of oxygen, a phenomenon known as the Warburg effect, which produces ATP via glycolysis. Increasing the conversion of pyruvate to lactate during aerobic glycolysis results in acidosis in the tumor microenvironments that facilitates invasion and metastasis of cancer cells (Shukla et al, 2014;Salamon et al, 2017;San-Millan and Brooks, 2017). However, metabolic plasticity is a newfound hallmark of cancer cells which shows that how different population of cancer cells within a tumor are using different metabolic pathways.…”

Section: Introductionmentioning

confidence: 99%

Histone Butyrylation/ Acetylation Remains Unchanged in Triple Negative Breast Cancer Cells after a Long Term Metabolic Reprogramming

Mehdikhani

Ghahremani

Nabati

et al. 2019

Asian Pac J Cancer Prev

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Background: Altered metabolism is one of the hallmarks of the cancer cells which reciprocally interrelate with epigenetic processes, such as post-translational histone modifications to maintain their desired gene expression profiles. The role of beta-hydroxybutyrate as a ketone body in cancer cell biology and histone modifications are reported. The present study aimed to evaluate the impacts of long-term metabolic reprogramming via glucose restriction and beta-hydroxybutyrate treatment on histone acetylation and butyrylation in MDA-MB231 cells as a model of triple negative stem-like breast cancer. Methods: For long-term treatment, cells were set up in three groups receiving DMEM with restricted glucose (250 mg/L), DMEM with restricted glucose but enriched with five millimolar beta-hydroxybutyrate and DMEM with standard glucose (1g\L) and investigated for a month. Histone modifications, including H3 acetylation and butyrylation, were investigated by immunoblotting after an acid extraction of the histone proteins. Results and Conclusion: Neither beta-hydroxybutyrate enrichment nor glucose restriction elicited a significant effect on the butyrylation or acetylation level of histone H3 upon a long-term treatment. Metabolic plasticity of cancer cells, mainly stem-like triple negative breast cancer cells alleviate or neutralize the impact of long-term metabolic reprogramming via restriction of glucose and histone modifications enrichment. These results shed new light upon the mechanism of controversial efficacy of ketogenic diets in clinical trials.

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“…ROS mediated PTEN oxidation results in promotion of breast cancer [134]. Additionally, ROS act as critical mediators that couple oxidative stress to aerobic glycolysis (Warburg effect) in cancer cells thereby favoring oncogenesis, and also link altered glucose metabolism to breast cancer stem cells and EMT phenotype [136][137][138].…”

Section: Reactive Oxygen Species and Oxidative Stressmentioning

confidence: 99%

Challenges and perspectives in the treatment of diabetes associated breast cancer

Samuel

Varghese

et al. 2018

Cancer Treatment Reviews

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Type 2 diabetes mellitus is one of the most common chronic disease worldwide and affects all cross-sections of the society including children, women, youth and adults. Scientific evidence has linked diabetes to higher incidence, accelerated progression and increased aggressiveness of different cancers. Among the different forms of cancer, research has reinforced a link between diabetes and the risk of breast cancer. Some studies have specifically linked diabetes to the highly aggressive, triple negative breast cancers (TNBCs) which do not respond to conventional hormonal/HER2 targeted interventions, have chances of early recurrence, metastasize, tend to be more invasive in nature and develop drug resistance. Commonly used anti-diabetic drugs, such as metformin, have recently gained importance in the treatment of breast cancer due to their proposed anti-cancer properties. Here we discuss the link between diabetes and breast cancer, the metabolic disturbances in diabetes that support the development of breast cancer, the challenges involved and future perspective and directions. We link the three main metabolic disturbances (dyslipidemia, hyperinsulinemia and hyperglycemia) that occur in diabetes to potential aberrant molecular pathways that may lead to the development of an oncogenic phenotype of the breast tissue, thereby leading to acceleration of cell growth, proliferation, migration, inflammation, angiogenesis, EMT and metastasis and inhibition of apoptosis in breast cancer cells. Furthermore, managing diabetes and treating cancer using a combination of anti-diabetic and classical anti-cancer drugs should prove to be more efficient in the treatment diabetes associated cancers.

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Glucose Metabolism in Cancer and Ischemia: Possible Therapeutic Consequences of the Warburg Effect

Cited by 16 publications

References 52 publications

Drp1 regulates mitochondrial dysfunction and dysregulated metabolism in ischemic injury via Clec16a-, BAX-, and GSH- pathways

Drp1 regulates mitochondrial dysfunction and dysregulated metabolism in ischemic injury via Clec16a-, BAX-, and GSH- pathways

Histone Butyrylation/ Acetylation Remains Unchanged in Triple Negative Breast Cancer Cells after a Long Term Metabolic Reprogramming

Challenges and perspectives in the treatment of diabetes associated breast cancer

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