Glutathione in Ovarian Cancer: A Double-Edged Sword

Nunes, Sónia; Serpa, Jacinta

doi:10.3390/ijms19071882

Cited by 84 publications

(69 citation statements)

References 112 publications

(139 reference statements)

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“…The determination of dynamic radical changes in cellular microenvironment with non-invasive approaches is an essential mean for assessing the effectiveness of anticancer agents on cancer treatment [45][46][47][48]. As mentioned above, 5-FU's chemotherapeutic properties are attributed to thymidylate synthase (TS) activity inhibition, to mitochondrial ROS generation and the caspases cascade activation [49].…”

Section: Discussionmentioning

confidence: 99%

Detection of Superoxide Alterations Induced by 5-Fluorouracil on HeLa Cells with a Cell-Based Biosensor

et al. 2019

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Background: In vitro cell culture monitoring can be used as an indicator of cellular oxidative stress for the assessment of different chemotherapy agents. Methods: A cell-based bioelectric biosensor was used to detect alterations in superoxide levels in the culture medium of HeLa cervical cancer cells after treatment with the chemotherapeutic agent 5-fluorouracil (5-FU). The cytotoxic effects of 5-fluorouracil on HeLa cells were assessed by the MTT proliferation assay, whereas oxidative damage and induction of apoptosis were measured fluorometrically by the mitochondria-targeted MitoSOX™ Red and caspase-3 activation assays, respectively. Results: The results of this study indicate that 5-FU differentially affects superoxide production and caspase-3 activation when applied in cytotoxic concentrations against HeLa cells, while superoxide accumulation is in accordance with mitochondrial superoxide levels. Our findings suggest that changes in superoxide concentration could be detected with the biosensor in a non-invasive and rapid manner, thus allowing a reliable estimation of oxidative damage due to cell apoptosis. Conclusions: These findings may be useful for facilitating future high throughput screening of different chemotherapeutic drugs with a cytotoxic principle based on free radical production.

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Section: Discussionmentioning

confidence: 99%

Detection of Superoxide Alterations Induced by 5-Fluorouracil on HeLa Cells with a Cell-Based Biosensor

et al. 2019

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“…Similarly, GSH plays an important role in cancer progression and resistance to therapy. Indeed, it is reported to be associated with chemoresistance to platinum salts, which is one of the main treatments for ovarian cancer [10]. Myo-inositol and phosphocholine (ChoP) have been reported in SKOV3 cells and their cellular concentrations reduced after treatment of Ptac2S, a novel anticancer agent [11].…”

Section: Discussionmentioning

confidence: 99%

A biochemical comparison of the lung, colonic, brain, renal, and ovarian cancer cell lines using 1H-NMR spectroscopy

Liu

Zhao

et al. 2020

Bioscience Reports

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Cancer cell lines are often used for cancer research. However, continuous genetic instability-induced heterogeneity of cell lines can hinder the reproducibility of cancer research. Molecular profiling approaches including transcriptomics, chromatin modification profiling, and proteomics are used to evaluate the phenotypic characteristics of cell lines. However, these do not reflect the metabolic function at the molecular level. Metabolic phenotyping is a powerful tool to profile the biochemical composition of cell lines. In the present study, 1H-NMR spectroscopy-based metabolic phenotyping was used to detect metabolic differences among five cancer cell lines, namely, lung (A549), colonic (Caco2), brain (H4), renal (RCC), and ovarian (SKOV3) cancer cells. The concentrations of choline, creatine, lactate, alanine, fumarate and succinate varied remarkably among different cell types. The significantly higher intracellular concentrations of glutathione, myo-inositol, and phosphocholine were found in the SKOV3 cell line relative to other cell lines. The concentration of glutamate was higher in both SKOV3 and RCC cells compared with other cell lines. For cell culture media analysis, isopropanol was found to be the highest in RCC media, followed by A549 and SKOV3 media, while acetone was the highest in A549, followed by RCC and SKOV3. These results demonstrated that 1H-NMR-based metabolic phenotyping approach allows us to characterize specific metabolic signatures of cancer cell lines and provides phenotypical information of cellular metabolism.

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“…This glutamine consumer phenotype may also be linked to cyst(e)ine dependency, as xCT concomitantly exports glutamate and imports cyst(e)ine. Glutamate is a direct product of glutamine degradation and maintaining the glutamine import sustains the import of cyst(e)ine, which has been related to increased therapy resistance in different cancer models [51], mostly due to its role in glutathione synthesis [52][53][54][55], for which glutamine-derived glutamate is also needed.…”

Section: Tca Cyclementioning

confidence: 99%

“…Riluzole interferes with glutamate flux and was shown to increase reactive oxygen species (ROS) by suppressing lactate dehydrogenase A (LDHA) and NAD+ [197]. Glutamate stimulates the glutamine import and glutaminolysis, sustaining the import of cyst(e)ine, which has been related to increased therapy resistance in different cancer models [51], mostly due to its role in glutathione synthesis [52,54]. Riluzole interferes with system xCT-cystine/glutamate antiporter, resulting in decreased GSH levels [197].…”

Section: New Therapies a Comprehensive Adjustment Of Therapy To The mentioning

confidence: 99%

Metabolic Remodelling: An Accomplice for New Therapeutic Strategies to Fight Lung Cancer

Mendes

Serpa

2019

Antioxidants

Self Cite

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Metabolic remodelling is a hallmark of cancer, however little has been unravelled in its role in chemoresistance, which is a major hurdle to cancer control. Lung cancer is a leading cause of death by cancer, mainly due to the diagnosis at an advanced stage and to the development of resistance to therapy. Targeted therapeutic agents combined with comprehensive drugs are commonly used to treat lung cancer. However, resistance mechanisms are difficult to avoid. In this review, we will address some of those therapeutic regimens, resistance mechanisms that are eventually developed by lung cancer cells, metabolic alterations that have already been described in lung cancer and putative new therapeutic strategies, and the integration of conventional drugs and genetic and metabolic-targeted therapies. The oxidative stress is pivotal in this whole network. A better understanding of cancer cell metabolism and molecular adaptations underlying resistance mechanisms will provide clues to design new therapeutic strategies, including the combination of chemotherapeutic and targeted agents, considering metabolic intervenients. As cancer cells undergo a constant metabolic adaptive drift, therapeutic regimens must constantly adapt.

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Glutathione in Ovarian Cancer: A Double-Edged Sword

Cited by 84 publications

References 112 publications

Detection of Superoxide Alterations Induced by 5-Fluorouracil on HeLa Cells with a Cell-Based Biosensor

Detection of Superoxide Alterations Induced by 5-Fluorouracil on HeLa Cells with a Cell-Based Biosensor

A biochemical comparison of the lung, colonic, brain, renal, and ovarian cancer cell lines using 1H-NMR spectroscopy

Metabolic Remodelling: An Accomplice for New Therapeutic Strategies to Fight Lung Cancer

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