Mitochondrial Effects on Seeds of Cancer Survival in Leukemia

El-Shaqanqery, Hend E.; Mohamed, Rania Hassan; Sayed, Ahmed A.

doi:10.3389/fonc.2021.745924

Cited by 4 publications

(4 citation statements)

References 113 publications

(125 reference statements)

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“…Of note, mitochondria are the chief site of ROS production, also the epicenter for autophagy and cell death. In abnormal circumstances such as cancer, infection, or derailed cell cycle, the ATP demand will be higher, which eventually forces the cell to synthesize ATP at a higher rate, which would result in excessive ROS generation ( El-Shaqanqery et al, 2021 ). The higher redox threshold of cancer cells indicates that mitochondria acclimatize to higher ROS concentration.…”

Section: Resultsmentioning

confidence: 99%

Dual Roles of Coconut Oil and Its Major Component Lauric Acid on Redox Nexus: Focus on Cytoprotection and Cancer Cell Death

et al. 2022

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It has been reported that coconut oil supplementation can reduce neuroinflammation. However, coconut oils are available as virgin coconut oil (VCO), crude coconut oil (ECO), and refined coconut oil (RCO). The impact of coconut oil extraction process (and its major fatty acid component lauric acid) at cellular antioxidant level, redox homeostasis and inflammation in neural cells is hitherto unexplained. Herein, we have shown the antioxidant levels and cellular effect of coconut oil extracted by various processes in human neuroblastoma cells (SH-SY5Y) cultured in vitro. Results indicate VCO and ECO treated cells displayed better mitochondrial health when compared to RCO. Similar trend was observed for the release of reactive oxygen species (ROS), key oxidative stress response genes (GCLC, HO-1, and Nqo1) and inflammatory genes (IL6, TNFα, and iNOS) in SH-SY5Y cells. Our results signified that both VCO and ECO offer better neural health primarily by maintaining the cellular redox balance. Further, RCO prepared by solvent extraction and chemical refining process lacks appreciable beneficial effect. Then, we extended our study to find out the reasons behind maintaining the cellular redox balance in neuroblastoma cells by VCO and ECO. Our GC-MS results showed that lauric acid (C14:0) (LA) content was the major difference in the fatty acid composition extracted by various processes. Therefore, we evaluated the efficacy of LA in SH-SY5Y cells. The LA showed dose-dependent effect. At IC50 concentration (11.8 μM), LA down regulated the oxidative stress response genes and inflammatory genes. The results clearly indicate that the LA inhibited the neuroinflammation and provided an efficient cellular antioxidant activity, which protects the cells. The efficiency was also evaluated in normal cell line such as fibroblasts (L929) to cross-validate that the results were not false positive. Different concentration of LA on L929 cells showed high compatibility. From our observation, we conclude that VCO and ECO offers better cellular protection owing to their powerful antioxidant system. Therefore, we advocate the inclusion of either VCO and/or ECO in the diet for a healthy lifestyle.

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Section: Resultsmentioning

confidence: 99%

Dual Roles of Coconut Oil and Its Major Component Lauric Acid on Redox Nexus: Focus on Cytoprotection and Cancer Cell Death

et al. 2022

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“…Additional metabolomic studies are needed to describe the conditions that drive leukemic cells to choose which TCA source contributes most to this OXPHOS activity because both amino acid ( 104 ) and fatty acid ( 105 ) oxidation have been implicated, demonstrating a high adaptability of their metabolism to ambient conditions. Hence, this metabolic flexibility is starting to be depicted in all the populations that we previously described—bulk cells ( 106 ), LSC ( 107 ) and chemoresistant cells ( 108 )—and it is important to consider because it hinders the possibility of using metabolism as a therapeutic target ( 109 ).…”

Section: Metabolism In Leukemia: Not As Simple As Originally Thoughtmentioning

confidence: 99%

Reactive Oxygen Species and Metabolism in Leukemia: A Dangerous Liaison

Romo-González

Ijurko²,

Hernández‐Hernández³

2022

Front. Immunol.

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Reactive oxygen species (ROS), previously considered toxic by-products of aerobic metabolism, are increasingly recognized as regulators of cellular signaling. Keeping ROS levels low is essential to safeguard the self-renewal capacity of hematopoietic stem cells (HSC). HSC reside in a hypoxic environment and have been shown to be highly dependent on the glycolytic pathway to meet their energy requirements. However, when the differentiation machinery is activated, there is an essential enhancement of ROS together with a metabolic shift toward oxidative metabolism. Initiating and sustaining leukemia depend on the activity of leukemic stem cells (LSC). LSC also show low ROS levels, but unlike HSC, LSC rely on oxygen to meet their metabolic energetic requirements through mitochondrial respiration. In contrast, leukemic blasts show high ROS levels and great metabolic plasticity, both of which seem to sustain their invasiveness. Oxidative stress and metabolism rewiring are recognized as hallmarks of cancer that are intimately intermingled. Here we present a detailed overview of these two features, sustained at different levels, that support a two-way relationship in leukemia. Modifying ROS levels and targeting metabolism are interesting therapeutic approaches. Therefore, we provide the most recent evidence on the modulation of oxidative stress and metabolism as a suitable anti-leukemic approach.

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“…Thus, it has been shown that calix [4]arene chalcone amide C-1011 is able to suppress the viability of 4T1 breast adenocarcinoma cells depending on their genetic context associated with the degree of malignancy. Mitochondria have been regarded as essential cell elements that fuel the metabolic needs of most cancer cell types [21]. Currently, it is well established that highly aggressive cancer cells rely on glycolysis instead of mitochondrial oxidative phosphorylation of glucose, and one marker of this metabotype known as the Warburg effect is a decrease in mitochondrial transmembrane potential [22][23].…”

Section: Resultsmentioning

confidence: 99%

Calix[4]arene chalcone amide C-1011 elicits differential effects on the viability of 4T1 mouse breast adenocarcinoma cells with different levels of adaptor protein Ruk/CIN85 expression

Babich¹,

Шлыков²,

Yesypenko³

et al. 2022

Ukr.Biochem.J.

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According to our earlier data, calix[4]arene chalcone amides modulate Ca ions exchange in the myometrium mitochondria and the level of inner membrane polarization that can potentially affect cell survival. To test this hypothesis, we studied the effect of calix[4]arene with 4 chalcone amide groups on mitochondria membrane polarization and viability of 4T1 mouse breast adenocarcinoma cells, a surrogate model of human triple-negative breast cancer, and on its highly malignant subline overexpressing the adaptor protein Ruk/CIN85. Mitochondria membrane potential was measured by flow cytometry, and cell viability was assessed using Trypan blue dye exclusion. It was shown that mitochondrial membranes of control (Mock) cells had a higher polarization level (67.80 ± 8.82 r.u., n = 5) compared to 4T1 cells with up-regulation of Ruk/CIN85 (RukUp cells) (25.42 ± 2.58 r.u., n = 4). Upon incubation of cells with 1 μM calix[4]arene C-1011, the CCCP-sensitive component of mitochondrial membranes polarization decreased (by almost 50%) in 4T1 Mock cells and did not change in RukUp cells compared with the control. It was demonstrated that 1 μM calix[4]arene C-1011 suppressed the viability of 4T1 Mock cells by 45%, but did not affect RukUp cells considerably. It was suggested that calix[4]arene chalcone amide С-1011 decreased mouse breast adenocarcinoma 4T1 cell viability at least by affecting mitochondrial membrane polarization.The data obtained indicate the prospects of further studies of calix[4]arene chalcone amide as a potential anticancer drug candidate.

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Mitochondrial Effects on Seeds of Cancer Survival in Leukemia

Cited by 4 publications

References 113 publications

Dual Roles of Coconut Oil and Its Major Component Lauric Acid on Redox Nexus: Focus on Cytoprotection and Cancer Cell Death

Dual Roles of Coconut Oil and Its Major Component Lauric Acid on Redox Nexus: Focus on Cytoprotection and Cancer Cell Death

Reactive Oxygen Species and Metabolism in Leukemia: A Dangerous Liaison

Calix[4]arene chalcone amide C-1011 elicits differential effects on the viability of 4T1 mouse breast adenocarcinoma cells with different levels of adaptor protein Ruk/CIN85 expression

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