Redox State In Cancer Cells Research Articles

Nanomaterials-Induced Redox Imbalance: Challenged and Opportunities for Nanomaterials in Cancer Therapy.

Cancer cells typically display redox imbalance compared with normal cells due to increased metabolic rate, accumulated mitochondrial dysfunction, elevated cell signaling, and accelerated peroxisomal activities. This redox imbalance may regulate gene expression, alter protein stability, and modulate existing cellular programs, resulting in inefficient treatment modalities. Therapeutic strategies targeting intra- or extracellular redox states of cancer cells at varying state of progression may trigger programmed cell death if exceeded a certain threshold, enabling therapeutic selectivity and overcoming cancer resistance to radiotherapy and chemotherapy. Nanotechnology provides new opportunities for modulating redox state in cancer cells due to their excellent designability and high reactivity. Various nanomaterials are widely researched to enhance highly reactive substances (free radicals) production, disrupt the endogenous antioxidant defense systems, or both. Here, the physiological features of redox imbalance in cancer cells are described and the challenges in modulating redox state in cancer cells are illustrated. Then, nanomaterials that regulate redox imbalance are classified and elaborated upon based on their ability to target redox regulations. Finally, the future perspectives in this field are proposed. It is hoped this review provides guidance for the design of nanomaterials-based approaches involving modulating intra- or extracellular redox states for cancer therapy, especially for cancers resistant to radiotherapy or chemotherapy, etc.

Targeting Hypoxic Tumor Plasticity for Recapturing Photodynamic‐Immunotherapy Sensitivity via Fluorinated Polysensitizers

AbstractMetabolic reprogramming is a key characteristics of tumor cells, mainly manifested by abnormal metabolism and tumor hypoxia. Here, the design of PolyFBODIPY characterized by the presence of BODIPY photosensitizers, fluorinated aliphatic chains as Oxygen affinity materials, and reactive oxygen species‐sensitive thioketal linkers is reported. PolyFBODIPY subsequently self‐assembles into NP@PolyFBODIPY which is capable of delivering oxygen and photosensitizers simultaneously and generating ROS under light irradiation, resulting in rapid polymer degradation and nanoparticle dissociation via breaking ROS‐sensitive thiol ketal linkers. NP@PolyFBODIPY can target hypoxic tumor plasticity to reprogram metabolism for recapturing photodynamic‐immunotherapy sensitivity for completely inhibiting tumor growth on multi‐drug‐resistant patient‐derived lung cancer xenografts (PDXMDR). Moreover, NP@PolyFBODIPY‐mediated photodynamic‐immunotherapy activates antitumor immune responses and effectively inhibits tumor growth and lung metastasis on an orthotropic metastatic triple‐negative breast cancer model. Mechanistically, metabolomics and lipidomics analysis reveals that NP@PolyFBODIPY‐mediated photodynamic‐immunotherapy not only destroys the redox state of cancer cells, but also affects the metabolism of lipid, amino acid, and d‐glutamine, thereby finally promoting autophagy and apoptosis and inhibiting the proliferation of cancer cells. These results highlight the potential of clinical translation of NP@PolyFBODIPY in targeting hypoxic tumor plasticity via oxygen supply, which reprograms the cellular metabolism for recapturing photodynamic‐immunotherapy sensitivity.

Interactions with stromal cells promote a more oxidized cancer cell redox state in pancreatic tumors.

Access to electron acceptors supports oxidized biomass synthesis and can be limiting for cancer cell proliferation, but how cancer cells overcome this limitation in tumors is incompletely understood. Nontransformed cells in tumors can help cancer cells overcome metabolic limitations, particularly in pancreatic cancer, where pancreatic stellate cells (PSCs) promote cancer cell proliferation and tumor growth. However, whether PSCs affect the redox state of cancer cells is not known. By taking advantage of the endogenous fluorescence properties of reduced nicotinamide adenine dinucleotide and oxidized flavin adenine dinucleotide cofactors we use optical imaging to assess the redox state of pancreatic cancer cells and PSCs and find that direct interactions between PSCs and cancer cells promote a more oxidized state in cancer cells. This suggests that metabolic interaction between cancer cells and PSCs is a mechanism to overcome the redox limitations of cell proliferation in pancreatic cancer.

In-vivo two-photon visualization and quantitative detection of redox state of cancer.

Glutathione (GSH), the most common and abundant antioxidant in the body, is particularly concentrated in cancer cells (2-10 mM). This concentration is approximately 1000 times that of normal cells, making GSH a specific tumor marker. Overexpression of GSH is critical for mapping the redox state of cancer cells. However, there are few probes and detection methods responsive to GSH that can quantitatively visualize GSH in vivo in two-photon excitation fluorescence (TPEF) imaging mode. The experimental results show that TPEF-GSH could not only target GSH in tumors, but also establish the quantitative relationship between TPEF signal and GSH concentration. We explored the optimal two-photon excitation wavelength of TPEF-GSH, the optimal cell incubation duration with TPEF-GSH, the best imaging time point for GSH in cells, and the quantitative relationship between the TPEF signal and the changes in GSH concentrations. In zebrafish embryo and zebrafish experiments, the ratiometric value of TPEF-GSH increased with the decrease of GSH concentration. Microinjection and co-incubation were used to verify whether the ratiometric value could quantify endogenous GSH in tumor-bearing zebrafish, and the obtained GSH levels were 4.66 mM and 5.16 mM, respectively. The ratio TPEF probe could accurately visualize and quantify GSH in vivo, reflecting the redox status of the tumor. The design of the ratiometric molecular probe provides a reliable strategy for the development of TPEF nanoprobe in vivo. In this article, a new GSH sensitive molecular probe, TPEF-GSH, has been developed with good specificity and sensitivity. TPEF-GSH was successfully used to image cancer cells in vitro and tumor-bearing zebrafish in vivo, and to further detect GSH levels.

Anticancer activity of flavonoids accompanied by redox state modulation and the potential for a chemotherapeutic strategy.

Since researchers began studying the mechanism of flavonoids' anticancer activity, little attention has been focused on the modulation of redox state in cells as a potential chemotherapeutic strategy. However, recent studies have begun identifying that the anticancer effect of flavonoids occurs both in their antioxidative activity which scavenges ROS and their prooxidative activity which generates ROS. Against this backdrop, this study attempts to achieve a comprehensive analysis of the individual and separate study findings regarding flavonoids' modulation of redox state in cancer cells. It focuses on the mechanism behind the anticancer effect, and mostly on the modulation of redox potential by flavonoids such as quercetin, hesperetin, apigenin, genistein, epigallocatechin-3-gallate (EGCG), luteolin and kaempferol in both in vitro and animal models. In addition, the clinical applications of and bioavailability of flavonoids were reviewed to help build a treatment strategy based on flavonoids' prooxidative potential.

Active colorimetric lipid-coated polyaniline nanoparticles for redox state sensing in cancer cells.

Herein, lipid-coated polyaniline (LiPAni) nanoparticles were fabricated to monitor the redox state of cancer cells. To confirm the characteristics of LiPAni, we firstly analyzed the size and chemical structures of the LiPAni nanoparticles. The absorbance properties of the LiPAni nanoparticles were observed to vary with the pH conditions. Furthermore, cell viability tests conducted with breast cancer cell lines showed that the cell viability of the cells with LiPAni nanoparticles was dramatically increased compared to those with the Tween80-coated polyaniline nanoparticles (TPAni) as a control. Subsequently, the colors of the LiPAni nanoparticles were observed and analyzed using spectroscopic methods. Finally, in order to investigate the more accurate sensing of the redox state using the color changes of the LiPAni nanoparticles with cancer cell lines, dark field microscopic images and scattering spectra were recorded at the single nanoparticle scale. For the TPAni nanoparticles, there was only a change in brightness and no change in color, but for the LiPAni nanoparticles, there was a change of color from yellow to pink in the dark field images.

Adaptation of Redox State in Cancer Cells that Survive Radiation

Adaptation of Redox State in Cancer Cells that Survive Radiation

A PET Glutamate Analogue to Measure Cancer Cell Redox State and Oxidative Stress: Promise and Paradox.

[18F]FSPG was shown to provide an indirect measure of the cellular redox state and may be used as an early indicator of therapy response to cancer therapies that cause oxidative stress. A somewhat paradoxical finding was that reduced [18F]FSPG cellular uptake was associated with either lower cellular concentrations of cystine or glutamate, despite opposing the transport of these substances in the Xc- antiporter, for which [18F]FSPG is also a substrate. Further studies of the kinetics of [18F]FSPG will help elucidate the factors mediating a decline in [18F]FSPG with oxidative stress.See related article by McCormick et al, p. 853.

Redox Paradox: A Novel Approach to Therapeutics-Resistant Cancer.

Cancer cells that are resistant to radiation and chemotherapy are a major problem limiting the success of cancer therapy. Aggressive cancer cells depend on elevated intracellular levels of reactive oxygen species (ROS) to proliferate, self-renew, and metastasize. As a result, these aggressive cancers maintain high basal levels of ROS compared with normal cells. The prominence of the redox state in cancer cells led us to consider whether increasing the redox state to the condition of oxidative stress could be used as a successful adjuvant therapy for aggressive cancers. Recent Advances: Past attempts using antioxidant compounds to inhibit ROS levels in cancers as redox-based therapy have met with very limited success. However, recent clinical trials using pro-oxidant compounds reveal noteworthy results, which could have a significant impact on the development of strategies for redox-based therapies. The major objective of this review is to discuss the role of the redox state in aggressive cancers and how to utilize the shift in redox state to improve cancer therapy. We also discuss the paradox of redox state parameters; that is, hydrogen peroxide (H2O2) as the driver molecule for cancer progression as well as a target for cancer treatment. Based on the biological significance of the redox state, we postulate that this system could potentially be used to create a new avenue for targeted therapy, including the potential to incorporate personalized redox therapy for cancer treatment.

ßNp63 controls cellular redox status.

A widely accepted hypothesis indicates that the accumulation of oxidative damage arising from endogenously produced reactive oxygen species (ROS) is one of the main triggers of cellular senescence, age-related disorders and cancer development. High ROS levels are responsible for lipid peroxidation, protein, and DNA oxidation, thus seriously threatening cellular fate and enhancing mutations risks [1]. The regulation of redox homeostasis is crucial to maintain a normal cellular function, ensuring cell proliferation and survival. An important protein, which is able to sustain epithelial proliferation/survival to counteract cellular senescence and organismal aging, is the transcription factor p63 [2]. TP63 belongs to the p53 gene family; it is expressed as multiple isoforms for the presence of two N-terminus promoters and C-terminus alternative splicing [2]. The sNp63 isoforms lack the N-terminal transactivation domain but they are still able to activate transcription of selected genes, using a second transactivation domain. sNp63 is responsible for activation of different cellular programs controlling cell proliferation potential and stemness, epithelial stratification, cell–cell, and cell-matrix adhesion [2, 3]. Interestingly, depletion of sNp63 in primary human keratinocytes and in cancer cell lines (lung, breast) increases endogenous ROS levels [4] suggesting that p63-dependent mechanisms are required in epithelial cells to control redox status. A recent study identified cytoglobin (CYGB) as a novel sNp63 target gene [4]. The role of CYGB in cellular metabolism is partially unknown, its expression increases under oxygen deficiency and oxidative stress. It binds oxygen, therefore it may facilitate oxygen diffusion to mitochondria. It detects O2 concentration in cells and protects them from ROS [4]. CYBG is co-expressed with sNp63 in the basal layer of the epidermis, the proliferative compartment, and in vitro, in proliferating keratinocytes. Down-modulation of CYGB in keratinocytes increases endogenous ROS levels, with consequent p53-mediated induction of apoptosis. The CYGB protecting role is also more evident upon oxidative stress, as CYGB-silenced keratinocytes undergoing to oxidative stress results in elevated level of ROS accumulation that parallel high level of apoptotic events. These results indicate that in physiological conditions, sNp63, via CYGB, plays an important role in maintaining physiological redox status. Thus, this could be one of the mechanisms engaged by sNp63 [4, 5], to counteract senescence/ageing and maintain high proliferative potential in epithelial stem cells. The redox status of cancer cells differs from that of normal cells and the modulation of oxidative stress is very relevant in both tumor formation and response to anti-cancer therapy. Indeed, high ROS levels in cancer cells are consequence of alteration in several signalling pathways that affect cellular metabolism. These ROS levels are balanced to elevated anti-oxidant defence pathways in cancer cells. Therefore, the role of ROS in tumorigenesis is still under debate: the increased anti-oxidant capacity suggests that high ROS level could contribute to a barrier against tumorigenesis, on the other hand, ROS may promote tumorigenesis by inducing DNA mutations and pro-oncogenic signalling [6–8]. The sNp63-CYGB axis could be part of this scenario, controlling cellular redox state in cancer cells. Indeed, experimental evidences show that CYGB-silenced lung SCC cells exhibit elevated ROS levels leading to apoptosis as well as an increased sensitivity to doxorubicin treatments [4]. Furthermore, computational analysis of lung cancer data sets, indicates that sNp63 and CYGB co-expression is a negative prognostic marker for patients, showing significant survival reduction. Glutathione peroxidase (GPX2) is another sNp63 direct target, which inhibits the activation of p53 by reducing the extent of oxidative stresses and oxidative stress-induced apoptosis in cancer cells [4]. In summary, sNp63 maintains redox cellular status in physiological condition, by direct transcriptional control of CYGB and GPX2, possibly preventing senescence/ageing and maintaining epithelial stem cells. Given that sNp63 is frequently amplified in tumors and acts in a dominant-negative manner over p53, sNp63 action as a pro-survival factor is, at least in part, mediated by the inhibition of the p53-dependent oxidative stress-induced apoptotic response. Furthermore, the sNp63-antioxidant properties may modulate therapeutic efficiency of anticancer treatments that act directly and/or indirectly regulating ROS levels.

Quantifying Single Human Cancer Cell Redox State By Scanning Electrochemical Microscopy

Scanning electrochemical microscopy (SECM) is increasingly applied to study and image live cells. Quantitative analyses of biological systems, however, still remain challenging. In the presented study, single human adenocarcinoma cervical cancer cells are electrochemically investigated by means of SECM. The target cell’s electrochemical signal is observed over time under the influence of green tea catechins (GTC), which are suggested to offer chemopreventive and therapeutic effects on cancer.1 The electrochemical response of living target cells is measured experimentally and the cell’s heterogeneous rate constant is determined by using a numerical model, based on forced convection during high speed SECM imaging. The beneficial effect of GTC on cancer cells could be confirmed by SECM and the presented study shows an alternative approach towards unravelling the mechanisms involved during inhibition of carcinogenesis. 1Connors, SK, Chornokur, G, Kumar NB (2012) Nutrition and Cancer, 64:4. Figure 1

Scanning electro-chemical microscopy reveals cancer cell redox state

Cancer cells show an abnormal balance of reduced/oxidised species and the detection of cancer redox balance can be exploited for diagnostic purposes. In particular, it is known that the expression of oncogenic Ras changes the intracellular oxidised/reduced glutathione balance. Electrochemical imaging of living cells is currently feasible by scanning electrochemical microscopy and was used here, using ferrocenemethanol as redox mediator, to measure the oxidised/reduced glutathione balance in human breast epithelial MCF10A cells expressing constitutively active Ha-Ras Val12 mutant compared to normal MCF10A cells. Oxidized ferrocenemethanol is reduced by glutathione and the resulting maps of current over cell cultures were different for transformed cells compared to normal cells. Furthermore, scanning electrochemical microscopy using ferrocenemethanol redox mediator was able to distinguish human lung carcinoma cells from the surrounding normal epithelium of clinical specimens. We propose that scanning electrochemical microscopy analysis using specific redox mediator such as ferrocenemethanol may become a useful tool in cancer diagnostics.

Reactive Oxygen Species in Cancer Biology and Anticancer Therapy

Reactive oxygen species (ROS) are a group of highly reactive chemicals under tight control of intracellular antioxidants. The balance in oxidation-antioxidation is essential for maintaining normal cell functions, and any imbalance could lead to a wide range of diseases including cancer. The intracellular level of ROS is generally elevated in cancer cells, revealing a critical role of ROS in the process of carcinogenesis and cancer progression. Conversely, there is also evidence showing that ROS can act as cancer suppressors. This may be due to the varying antioxidant capacities of different cancers. These findings indicate a complex redox state in cancer cells. In this review we summarize the main features of ROS and their functions with respect to cancer initiation, hallmarks of cancer, and signaling in cancer cells. ROS-elevating and ROS-depleting anticancer strategies and their mechanisms are thoroughly discussed. We argue that the rationale for therapy choice depends on a complete understanding of cancer cell redox state, namely, the "redox signaling signature" of cancer.

CHOP THERAPY INDUCED MITOCHONDRIAL REDOX STATE ALTERATION IN NON-HODGKIN'S LYMPHOMA XENOGRAFTS.

We are interested in investigating whether cancer therapy may alter the mitochondrial redox state in cancer cells to inhibit their growth and survival. The redox state can be imaged by the redox scanner that collects the fluorescence signals from both the oxidized-flavoproteins (Fp) and the reduced form of nicotinamide adenine dinucleotide (NADH) in snap-frozen tissues and has been previously employed to study tumor aggressiveness and treatment responses. Here, with the redox scanner we investigated the effects of chemotherapy on mouse xenografts of a human diffuse large B-cell lymphoma cell line (DLCL2). The mice were treated with CHOP therapy, i.e., cyclophosphamide (C) + hydroxydoxorubicin (H) + Oncovin (O) + prednisone (P) with CHO administration on day 1 and prednisone administration on days 1-5. The Fp content of the treated group was significantly decreased (p = 0.033) on day 5, and the mitochondrial redox state of the treated group was slightly more reduced than that of the control group (p = 0.048). The decrease of the Fp heterogeneity (measured by the mean standard deviation) had a border-line statistical significance (p = 0.071). The result suggests that the mitochondrial metabolism of lymphoma cells was slightly suppressed and the lymphomas became less aggressive after the CHOP therapy.

Repressing malic enzyme 1 redirects glucose metabolism, unbalances the redox state, and attenuates migratory and invasive abilities in nasopharyngeal carcinoma cell lines

A large amount of nicotinamide adenine dinucleotide phosphate (NADPH) is required for fatty acid synthesis and maintenance of the redox state in cancer cells. Malic enzyme 1 (ME1)-dependent NADPH production is one of the three pathways that contribute to the formation of the cytosolic NADPH pool. ME1 is generally considered to be overexpressed in cancer cells to meet the high demand for increased de novo fatty acid synthesis. In the present study, we found that glucose induced higher ME1 activity and that repressing ME1 had a profound impact on glucose metabolism of nasopharyngeal carcinoma (NPC) cells. High incorporation of glucose and an enhancement of the pentose phosphate pathway were observed in ME1-repressed cells. However, there were no obvious changes in the other two pathways for glucose metabolism: glycolysis and oxidative phosphorylation. Interestingly, NADPH was decreased under low-glucose condition in ME1-repressed cells relative to wild-type cells, whereas no significant difference was observed under high-glucose condition. ME1-repressed cells had significantly decreased tolerance to low-glucose condition. Moreover, NADPH produced by ME1 was not only important for fatty acid synthesis but also essential for maintenance of the intracellular redox state and the protection of cells from oxidative stress. Furthermore, diminished migration and invasion were observed in ME1-repressed cells due to a reduced level of Snail protein. Collectively, these results suggest an essential role for ME1 in the production of cytosolic NADPH and maintenance of migratory and invasive abilities of NPC cells.

Reductive Carboxylation May Affect Redox State of Cancer Cells

Processing of traditional Chinese medicine (TCM) can enhance the efficacy and/or reduce the toxicity. Currently available approaches regarding TCM processing generally focus on a few markers, rendering a one-sided strategy that fail to unveil the involved global chemical transformation. We herein present a strategy, by integrating enhanced multicomponent characterization, untargeted metabolomics, and mass spectrometry imaging (MSI), to visualize the chemical transformation and identify the markers associated with the wine steaming of Ligustri Lucidi Fructus (LLF), as a case. An ultra-high-performance liquid chromatography/quadrupole-Orbitrap mass spectrometry-based polarity-switching (between the negative and positive modes), precursor ions list-including data-dependent acquisition approach was developed, which enabled the simultaneous targeted/untargeted characterization of 158 components from LLF via one injection analysis. Holistic, continuous, and time-dependent chemical variation trajectory, among different processing time (0–12 h) for LLF, was depicted by principle component analysis. Pattern recognition chemometrics could unveil 20 markers, among which the peak area ratios of eight components to oleuropein aglycone, used as an internal standard, were diagnostic to identify the processed (both the commercial and in-house prepared) from the raw LLF. Four markers (10-hydroxyoleoside dimethylester, 8-demethyl-7-ketoliganin, elenolic acid, and salidroside) showed an increasing trend, while another four (neonuezhenide/isomer, verbascoside/isomer, luteoline, and nuzhenal A) decreased in LLF after processing. MSI visualized the spatial distribution in the fruit and indicated consistent variation trends for four major markers deduced by the untargeted metabolomics approach. This integral strategy, in contrast to the conventional approaches, gives more convincing data supporting the processing mechanism investigations of TCM from a macroscopic perspective.

Influence of reductive carboxylation on redox state of cancer cells

Influence of reductive carboxylation on redox state of cancer cells

Distinct Redox Profiles of Selected Human Prostate Carcinoma Cell Lines: Implications for Rational Design of Redox Therapy

The effects of several cancer chemotherapeutic drugs and radiation are mediated, at least in part, by oxidative stress. To better understand this process, we analyzed certain biochemical properties affecting reduction-oxidation (redox) balance in normal prostate epithelial cells and several prostate cancer cell lines. Highly aggressive androgen-independent prostate cancer PC3 cells demonstrated significantly higher levels of total antioxidant capacity (AC) and intra- and extracellular glutathione (GSH)/glutathione disulfide (GSSG) ratios when compared with normal prostate epithelial PrEC cells. WPE1-NB26 cells, a prostate cancer cell line derived from immortalized RWPE1 human prostate epithelial cells, demonstrated significantly higher levels of total AC and intra- and extracellular GSH/GSSG ratios, but lower levels of intracellular reactive oxygen/nitrogen species and lipid peroxidation compared with RWPE1 cells. LNCaP-C4-2 cells, a more aggressive prostate cancer derived from less aggressive androgen-responsive LNCaP cells, exhibited higher levels of AC and extracellular GSH/GSSG ratio when compared to LNCaP cells. Specific cell types showed distinct cytotoxic responses to redox-modulating compounds. WPE1-NB26 cells were more sensitive to phenethyl isothiocyanate and tumor necrosis factor (TNF) than RWPE1 cells, while PC3 cells were more sensitive to TNF than PrEC cells. These results are consistent with the hypothesis that cancer cell redox state may modulate responses to redox-modulating therapeutic regimens.

Assessing multidrug resistance protein 1-mediated function in cancer cell multidrug resistance by scanning electrochemical microscopy and flow cytometry

Cancer cell multidrug resistance is a molecular signature that highly influences the outcome of chemotherapy treatment and for which there is currently no robust method to monitor in vitro its activity. Herein, we demonstrate that ferrocenemethanol (FcCH 2OH) and its oxidized form ([FcCH 2OH] +) affect the redox state of cancer cells. Specifically, the interaction of FcCH 2OH with the glutathione couple (GSH/GSSG) is shown in human adenocarcinoma cervical cancer cells HeLa and a multidrug resistant variant overexpressing the multidrug resistant associated protein 1 (MRP1) using bioanalytical techniques, such as flow cytometry and fluorescence microscopy. It is further demonstrated that the differential response to FcCH 2OH in multidrug-resistant cells is in part due to MRP1's unspecific efflux. Scanning electrochemical microscopy confirmed the interaction between FcCH 2OH and the cells, and the differential response was observed to depend on MRP1 expression. This newly established relation between FcCH 2OH/[FcCH 2OH] +, GSH/GSSG and multidrug resistance in human cancer cells enables than the acquisition of scanning electrochemical microscopy images.

The anti-oxidant capacity of tumour glycolysis

Purpose: In this mini-review data are summarised which provide evidence for the biological and clinical significance of tumour glycolysis and of its relationship to the redox state of cancer cells.Results: Malignant transformation is associated with an overexpression of numerous glycolysis-related genes in the vast majority of human cancers. At the same time, glycolytic activity and glycolysis-linked metabolic milieu are often variable between individual tumours which induces large variations in treatment response and aggressiveness. Currently, there is no genetic or proteomic marker for the prediction of the therapeutic response for individual tumours, but the prognostic value of tumour lactate accumulation for the emergence of metastasis, for patient survival and for radioresistance has been documented in a number of studies.Conclusions: Transactivation of tumour glycolyis appears to generate a chemically reduced milieu associated with an inhibition of ROS (reactive oxygen species) -mediated fixation of DNA damage and induction of radioresistance. Furthermore, highly glycolytic cells enhance the antioxidant defense via glutathione, and pyruvate can be decarboxylated non-enzymatically upon reducing hydrogen peroxide. The summary of data given here emphasises the importance of further research efforts on the link between carbohydrate metabolism and redox state of cancer cells.