ARTICLE | doi:10.20944/preprints202111.0313.v1
Subject: Medicine & Pharmacology, Pathology & Pathobiology Keywords: PRDX6; inflammation; NRF2; HGFs.
Online: 17 November 2021 (23:34:15 CET)
Periodontitis is a progressive and inflammatory oral disease and results in the damage of the supporting tissues of teeth. Peroxiredoxin6 (PRDX6) is an antioxidant enzyme and has been identified as a regulator in redox balance. This study aimed to investigate whether PRDX6 could protect human gingival fibroblasts (HGFs) from lipopolysaccharide (LPS) induced inflammation and its mechanisms. Here, both inflamed and non-inflamed human gingival tissues were collected to assess the expression of PRDX6 and NRF2 by Immunohistochemistry and Western blotting. Furthermore, HGFs were stimulated with LPS, MJ33 (PRDX6 phospholipase A2 inhibitor), or ML385 (NRF2 inhibitor). The expression levels of inflammatory cytokines were measured by RT-qPCR and ELISA, and reactive oxygen species (ROS) was detected using DCFH-DA. PRDX6 was downregulated in inflamed gingival tissues. In HGFs, LPS induced inflammatory cytokines and ROS was upregulated in PRDX6 knockdown cells. Furthermore, co-treatment with MJ33 alleviated LPS-induced inflammatory cytokines and ROS, while inhibiting NRF2 upregulated those in HGFs. Therefore, this study provided a new mechanistic insight that PRDX6, regulated by the NRF2 signaling, alleviates LPS- induced periodontitis in human gingival fibroblasts.
REVIEW | doi:10.20944/preprints202102.0107.v1
Online: 3 February 2021 (10:09:39 CET)
Pancreatic cancer is a fatal disease with mortality rate of 5% and a with a limited survival rate of 5 years. Despite of the extensive efforts that has been made to cure the disease it still has been considered as ‘undruggable’. It is characterized by epithelial to dense stromal tumor formation however due to lack of diagnosis options and treatment test available to detect the disease to the point at which resection of the tumor is possible, it makes it the fourth leading cause of cancer related death. The unavailable information regarding the early detection of biological markers along with the increased invasive tumor, the inherit chemoresistance against medication radiation and chemotherapy stubbornly fail the therapeutic options available. These associated problems made the scientists to reevaluate the approaches that are currently in practice and take a step back to fully understand the basic biological pathways that are involved in the pancreatic cancer, the heterogeneity of the tumor itself along with expression and a number of mutations that are observed at different locations. Clinical trial along with new approaches are nowadays focus of research to treat this tumor. The review paper describes the basic cellular pathways involved in pancreatic cancer, the gene mutations and their expression having effect on the pathology of the diseases along with treatment options that are available to treat the tumor. These efforts will help with the expansion of our knowledge to undergo the clinical trial and the synthesis of novel medicines for the prognosis of the disease.
ARTICLE | doi:10.20944/preprints202112.0161.v1
Online: 9 December 2021 (15:46:41 CET)
Cells that experience high levels of oxidative stress respond with the induction of antioxidant proteins through the activation of the transcription factor Nrf2. Nrf2 is negatively regulated by Keap1 which binds to Nrf2 to facilitate its ubiquitination and ensuing proteasomal degradation under basal conditions. Here, we study protein folding and misfolding in Nrf2 and Keap1 in yeast, mammalian cells, and purified proteins under oxidative stress conditions. Both Nrf2 and Keap1 are susceptible to protein misfolding and inclusion formation upon oxidative stress. We propose that the intrinsically disordered regions within Nrf2 and the high cysteine content of Keap1 contribute to their oxidation and the ensuing misfolding. Our work reveals previously unexplored aspects of Nrf2 and Keap1 regulation and dysregulation by oxidation-induced protein misfolding.
ARTICLE | doi:10.20944/preprints201611.0093.v1
Subject: Life Sciences, Molecular Biology Keywords: diabetes mellitus; cardiomyopathy; hyperglycemia; oxidative stress; aspalathin; Nrf2
Online: 17 November 2016 (11:07:56 CET)
Aspalathin (ASP) can protect H9c2 cardiomyocytes against high glucose (HG)-induced shifts in myocardial substrate preference, oxidative stress and apoptosis. While the protective mechanism of aspalathin remains unknown, nuclear factor (erythroid-derived 2)-like 2 (Nrf2) has emerged as a key factor for intracellular responses against oxidative stress. Therefore, we hypothesized that aspalathin protects the myocardium against hyperglycemia-induced oxidative damage by up-regulating Nrf2 expression in H9c2 cardiomyocytes and diabetic (db/db) mice. Using an oxidative stress RT2 Profiler PCR array, ASP at a dose of 1 µM was demonstrated to protect H9c2 cardiomyocytes against HG-induced oxidative stress, but silencing of Nrf2 abolished this protective response of ASP and exacerbated cardiomyocyte apoptosis. Db/db mice and their non-diabetic (db/+) littermate controls were subsequently treated daily for 6 weeks with either a low (13 mg/kg) or high (130 mg/kg) ASP dose. Compared to nondiabetic mice the db/db mice presented increased cardiac remodeling and enlarged left ventricular wall that occurred concomitant to enhanced oxidative stress. Daily treatment of mice with ASP at a dose of 130 mg/kg for 6 weeks was more effective at reversing complications than both a low dose ASP or metformin, eliciting enhanced expression of Nrf2 and its downstream antioxidant genes. These results indicate that ASP maintains cellular homeostasis and protects the myocardium against hyperglycemia-induced stress through activation of Nrf2 and its downstream target genes.
REVIEW | doi:10.20944/preprints201809.0171.v1
Subject: Biology, Physiology Keywords: NOX, sulfenylation, Nrf2, SKN-1, centenarians, extracellular matrix, longevity
Online: 10 September 2018 (12:59:22 CEST)
An accumulating body of evidence suggests that physiological reactive oxygen species (ROS) generated by NADPH oxidases act as a redox signal to re-establish homeostasis, a capacity that progressively declines during aging, but is maintained in long-lived animals to promote healthy aging. In the model organism Caenorhabditis elegans, ROS generated by dual oxidases (Duox) are important for extracellular matrix integrity, pathogen defense, oxidative stress resistance, and longevity. The Duox enzymatic activity is tightly regulated and under cellular control. Developmental molting cycles, pathogen infections, toxins, mitochondrial-derived ROS, drugs, and small GTPases (RHO-1) can activate Duox (BLI-3) to generate ROS, whereas NADPH oxidase inhibitors and negative regulators, such as MEMO-1, can inhibit Duox to generate ROS. Three mechanisms-of-action have been discovered for the Duox/BLI-3-generated ROS: 1) enzymatic activity to catalyze cross-linking of free tyrosine ethyl ester in collagen bundles to stabilize extracellular matrices, 2) high ROS bursts/levels to kill pathogens, and 3) Redox signaling activating downstream kinase cascades to transcription factors orchestrating oxidative stress- and immunity responses to re-establish homeostasis. Although Duox function at the cell surface is well established, recent genetic and biochemical data also suggests a novel role for Duoxs at the endoplasmic reticulum membrane to control redox signaling. Evidence underlying these mechanisms initiated by ROS from NADPH oxidases and their relevance for human aging are discussed in this review. Appropriately controlling NADPH oxidase activity for local and physiological redox signaling to maintain cellular homeostasis might be a therapeutic strategy to promote healthy aging.
REVIEW | doi:10.20944/preprints202209.0354.v1
Subject: Medicine & Pharmacology, Other Keywords: Wound healing; metastasis; oxidative stress; macrophage; HIF; NF-kB; Nrf2
Online: 23 September 2022 (03:28:28 CEST)
Many signaling pathways, molecular and cellular actors which are critical for wound healing have been implicated in cancer metastasis. These two conditions are a complex succession of cellular biological events and accurate regulation of these events is essential. Apart from inflammation, macrophages-released ROS arise as major regulators of these processes. But, whatever the pathology concerned, oxidative stress is a complicated phenomenon to control and requires a finely tuned balance over the different stages and responding cells. This review provides an overview of the pivotal role of oxidative stress in both wound healing and metastasis, encompassing the contribution of macrophages. Indeed, macrophages are major ROS producers but also appear as their targets since ROS interfere with their differentiation and function. Elucidating ROS functions in wound healing and metastatic spread may allow the development of innovative therapeutic strategies involving redox modulators.
ARTICLE | doi:10.20944/preprints202207.0152.v1
Subject: Life Sciences, Cell & Developmental Biology Keywords: Alzheimer’s disease; oxidative stress; presenilin; mitochondria; calcium; neuronal dysfunction; Nrf2
Online: 11 July 2022 (08:03:08 CEST)
A Mitochondrial dysfunction and oxidative stress are major contributors to the pathophysiology of neurodegenerative diseases, including Alzheimer’s disease (AD). However, the mechanisms driving mitochondrial dysfunction and oxidative stress are unclear. Familial AD (fAD) is an early onset form of AD caused primarily by mutations in the presenilin-encoding genes. Previously, using Caenorhabditis elegans as a model system to study presenilin function, we found that loss of C. elegans presenilin orthologue, SEL-12, results in elevated mitochondrial and cytosolic calcium levels. Here, we provide evidence that elevated neuronal mitochondrial generated reactive oxygen species (ROS) and subsequent neurodegeneration in sel-12 mutants are a consequence of the increase of mitochondrial calcium levels and not cytosolic calcium levels. We also identify mTORC1 signaling as a critical factor in sustaining high ROS in sel-12 mutants in part through its repression of the ROS scavenging system SKN-1/Nrf. Our study reveals that SEL-12/presenilin loss disrupts neuronal ROS homeostasis by increasing mitochondrial ROS generation and elevating mTORC1 signaling, which exacerbates this imbalance by suppressing SKN-1/Nrf antioxidant activity.
ARTICLE | doi:10.20944/preprints202202.0320.v1
Subject: Medicine & Pharmacology, General Medical Research Keywords: Neurodegenerative disease; DJ-1; RNA-seq; Nrf2 signaling; lncRNA; MALAT1
Online: 25 February 2022 (02:40:02 CET)
Microglia activation causes neuroinflammation, which is a hallmark of neurodegenerative disorders, brain injury, and aging. Ladostigil, a bifunctional reagent with antioxidant and anti-inflammatory properties, reduced microglial activation and enhanced brain functioning in elderly rats. In this study, we studied SH-SY5Y, a human neuroblastoma cell line, and tested viability in the presence of hydrogen peroxide and Sin1 (3-morpholinosydnonimine), which generates reactive oxygen and nitrogen species (ROS/RNS). Both stressors caused significant apoptosis and necrotic cell death that was attenuated by ladostigil. Our results from RNA-seq experiments show that long non-coding RNAs (lncRNAs) account for 30% of all transcripts in SH-SY5Y cells treated with Sin1 for 24 hours. Altogether, we identify 94 differently expressed lncRNAs in the presence of Sin1, including MALAT1, a highly expressed lncRNA with anti-inflammatory and anti-apoptotic functions. Additional activities of Sin-1 upregulated lncRNAs include redox homeostasis (e.g., MIAT, GABPB1-AS1), energy metabolism (HAND2-AS1), and neurodegeneration (e.g., MIAT, GABPB1-AS1, NEAT1). Four lncRNAs implicated as enhancers were significantly upregulated in cells exposed to Sin1 and ladostigil. Finally, we show that H2O2 and Sin1 increased the expression of DJ-1, a redox sensor and modulator of Nrf2 (nuclear factor erythroid 2–related factor 2). Nrf2 (NFE2L2 gene) is a major transcription factor regulating antioxidant genes. In the presence of ladostigil, DJ-1 expression is restored to its baseline. The mechanisms governing SH-SY5Y cell survival and homeostasis are highlighted by the beneficial role of ladostigil in the crosstalk involving Nrf2, antioxidant transcription factor DJ-1, and lncRNAs. Stress-dependent induction of lncRNAs represents an underappreciated regulatory level that contributes to cellular homeostasis and the capacity of SH-SY5Y to cope with oxidative stress.
ARTICLE | doi:10.20944/preprints202009.0194.v1
Subject: Life Sciences, Molecular Biology Keywords: Oenothera biennis; Evening primrose; Oxidative stress; Cell death; Nrf2/HO-1
Online: 9 September 2020 (03:29:52 CEST)
Background: Oenothera biennis (evening primrose) produces bioactive substances with a diverse range of pharmacological functions. However, it is currently unknown whether extract prepared from the aerial parts of O. biennis (APOB) can protect the skin against oxidative stress. To investigate the protective effects of APOB against oxidative stress-induced damage in human skin keratinocytes (HaCaT) and elucidate the underlying mechanisms. Methods: We pretreated HaCaT cells with various concentrations of APOB or the antioxidant N-acetyl-L-cysteine before applying H2O2. We then compared the cell viability, intracellular reactive oxygen species (ROS) production, and DNA and mitochondrial damage between pretreated and untreated control cells using a range of assays, flow cytometry, and Western blot analysis and also examined the reducing power and DPPH free radical-scavenging activity of APOB. Results: APOB pretreatment significantly increased cell viability, effectively attenuated H2O2-induced comet tail formation, and inhibited H2O2-induced phosphorylation of the histone γH2AX, as well as the number of apoptotic bodies and Annexin V-positive cells. APOB was found to have a high reducing power and DPPH radical-scavenging activity and also exhibited scavenging activity against intracellular ROS accumulation and restored the loss of mitochondrial membrane potential caused by H2O2. APOB pretreatment almost totally reversed the enhanced cleavage of caspase-3, the degradation of poly (ADP-ribose)-polymerase (PARP), DNA fragmentation that usually occurs in the presence of H2O2 and increased the levels of heme oxygenase-1 (HO-1), a potent antioxidant enzyme that is associated with the induction of nuclear factor-erythroid 2-related factor 2 (Nrf2). Conclusions: APOB can protect HaCaT cells from H2O2-induced DNA damage and cell death by blocking cellular damage related to oxidative stress via a mechanism that affects ROS elimination and by activating the Nrf2/HO-1 signaling pathway.
REVIEW | doi:10.20944/preprints202009.0684.v1
Subject: Medicine & Pharmacology, Allergology Keywords: Clinical application; dimethyl fumarate; disease; fumaric acid esters; oxidative stress; inflammation; Nrf2; disease
Online: 28 September 2020 (11:03:25 CEST)
Fumaric acid esters (FAEs) are small molecules with anti-oxidative, anti-inflammatory and immune-modulating effects. Dimethyl fumarate (DMF) is the best characterised FAE and is approved and registered for the treatment of psoriasis and Relapsing-Remitting Multiple Sclerosis (RRMS). Psoriasis and RRMS share an immune-mediated aetiology, driven by severe inflammation and oxidative stress. DMF, as well as monomethyl fumarate and diroximel fumarate, are commonly prescribed first-line agents with favourable safety and efficacy profiles. The potential benefits of FAEs against other diseases that appear pathogenically different but share the pathologies of oxidative stress and inflammation are currently investigated.
ARTICLE | doi:10.20944/preprints201902.0083.v1
Subject: Life Sciences, Molecular Biology Keywords: Cognitive decline, Epigenetics, Epigenetic inheritance, Methylation, Nrf2, NF-kβ, Oxidative stress, Inflammation, resveratrol, SAMP8
Online: 11 February 2019 (08:56:08 CET)
A variety of environmental factors contribute significantly to age-related cognitive decline and Alzheimer’s Disease (AD). Nutrition can alter epigenetics, improving health outcomes, which transmitted across generations; this process is called epigenetic inheritance. We investigate the beneficial effects of maternal resveratrol supplementation in offspring. We feed females SAMP8 with resveratrol-enriched diet during two months prior to mating. Direct exposed F1 generation and the transgenerational F2 generation were investigated. Object novel recognition and Morris water maze demonstrated improvements in cognition in the 6-month-old F1 and F2 generations from resveratrol fed mothers. A significant increase in global DNA methylation with a decrease in hydroxymethylation in F1 and F2 were found. Accordingly, Dnmt3a/b and Tet2 gene expression changed. Methylation levels of Nrf2 and NF-kβ genes promoters raised in offspring, inducing changes in target genes expression, as well as hydrogen peroxide levels. Offspring resulted from resveratrol fed mother showed increase AMPKα activation, mTOR inhibition and an increase in Pgc-1α gene expression and Beclin-1 protein levels. Endoplasmic reticulum stress sensors were found changed both in F1 and F2 generations. Overall, our results demonstrated that maternal resveratrol supplementation could prevent cognitive impairment in the SAMP8 mice offspring through epigenetic changes and cell signaling pathways.
REVIEW | doi:10.20944/preprints201702.0047.v1
Subject: Medicine & Pharmacology, Nutrition Keywords: advanced glycation end products; fructose; glucose; lipogenesis; sphingolipids; NLRP3; Nrf2; mitochondrial dysfunction; oxidative stress
Online: 14 February 2017 (08:38:14 CET)
The rapid increase in metabolic diseases occurred in the last three decades in both industrialized and developing countries has been related to the rise in sugar-added foods and sweetened beverages consumption. An emerging topic in the pathogenesis of metabolic diseases related to modern nutrition is the role of Advanced Glycation Endproducts (AGEs). AGEs can be ingested with high temperature processed foods, but also endogenously formed as consequence of a high dietary sugars intake. Animal models of high sugars consumption, in particular fructose, have reported AGEs accumulation in different tissues in association with peripheral insulin resistance and lipid metabolism alterations. The in vitro observation that fructose is one of the most rapid and effective glycating agent when compared to other sugars has prompted the investigation of the in vivo fructose-induced glycation. In particular, the widespread employment of fructose as sweetener has been ascribed by many experimental and observational studies for the enhancement of lipogenesis and intracellular lipid deposition. Indeed, diet-derived AGEs have been demonstrated to interfere with many cell functions such as lipid synthesis, inflammation, antioxidant defences, and mitochondrial metabolism. Moreover, emerging evidences also in humans suggest that this impact of dietary AGEs on different signalling pathways can contribute to the onset of organ damage in liver, skeletal and cardiac muscle, and brain, affecting not only metabolic control, but global health. Indeed, the here reviewed most recent reports on the effects of high sugars consumption and diet-derived AGEs on human health suggest the need to limit the dietary sources of AGEs, including added sugars, to prevent the development of metabolic diseases and related comorbidities.
REVIEW | doi:10.20944/preprints201811.0016.v1
Subject: Medicine & Pharmacology, Nutrition Keywords: wine; mediterranean diet; okinawa diet; health; nrf2; alcohol; polyphenols; hormesis; cardiovascular protection; cancer; Alzheimer; metabolic disease
Online: 2 November 2018 (05:08:46 CET)
Hippocrate, the father of medicine, already said:"Wine is a thing wonderfully appropriate to man if, in health as in disease, it is administered with appropriate and just measure according to the individual constitution." wine has always accompanied humanity, for religion or for health. Christians and Jews need wine for the liturgy. For Platon the wine was an indispensable element in society and took all its importance in the symposium. In this second part of the banquet, mixed with water, the wine gave the word. If the french paradox made a lot of ink flow; it was the wine that was originally responsible for it. Many researchers have tried to share the alcohol and polyphenols in order to solve the mystery. Beyond its cardiovascular effects, there are also effects on longevity, metabolism, cancer prevention and neuroprotection, and the list goes on. The purpose of this work is to make an analysis of current knowledge on the subject. Indeed, if the paradigm of the antioxidants is seductive, it is perhaps by their prooxidant effect that the polyphenols could act, by an epigenetic process mediated by nrf2. Wine is a preserve of antioxidants for the winter and it is by this property that the wine acts, in alcoholic solution. A wine without alcohol is pure heresy. By the way, we were not talking about elixir to design all this millennial pharmacopee that made the man was able to heal and prosper on the planet. From Alvise Cornaro to Serge Renaud, nutrition was the key to health and longevity, whether Cretan or Okinawa diet, it is the small dose of alcohol (wine or sake) that allows the bioavailability of polyphenols. Moderate drinking give a protection for diseases and a longevity potential. In conclusion, let’s drink fewer, but drink better to live older.
ARTICLE | doi:10.20944/preprints201612.0042.v1
Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: acute lung injury; mycelium of Sanghuangporus sanghuang; lipopolysaccharide; KAP1/Nrf2 pathway; PI3K/Akt/mTOR pathways; HO-1; HNGB1
Online: 7 December 2016 (11:15:30 CET)
Acute lung injury (ALI) is characterized by inflammation of the lung tissue and oxidative injury caused by excessive accumulation of reactive oxygen species. Studies have suggested that anti-inflammatory or antioxidant agents could be used for the treatment of ALI with a good outcome. Therefore, our study aimed to test whether the mycelium extract of Sanghuangporus sanghuang (SS-1), believed to exhibit antioxidant and anti-inflammatory properties, could be used against the excessive inflammatory response associated with LPS-induced ALI in mice and to investigate its possible mechanism of action. The experimental results showed that the administration of SS-1 could inhibit LPS-induced inflammation. SS-1 could reduce the number of inflammatory cells, inhibit MPO activity, regulate the TLR4/PI3K/Akt/mTOR pathway and the signal transduction of NF-κB and MAPK pathways in the lung tissue, and inhibit HNGB1 activity in BALF. In addition, SS-1 could affect the synthesis of antioxidant enzymes HO-1 and Trx-1 in the lung tissue and regulate signal transduction in the KAP1/Nrf2/Keap1 pathway. Histological results showed that administration of SS-1 prior to induction could inhibit the large-scale LPS-induced neutrophil infiltration of the lung tissue. Therefore, based on all experimental results, we propose that SS-1 exhibits a protective effect against LPS-induced (ALI) in mice. The mycelium of S. sanghuang can potentially be used for the treatment or prevention of inflammation-related diseases
ARTICLE | doi:10.20944/preprints202105.0132.v1
Subject: Life Sciences, Biochemistry Keywords: aqueous fullerene dispersions; pristine fullerenes; metallofullerenes; ROS homeostasis; oxidative stress; NOX4; Nrf2; PRAR-γ; heme oxygenase 1; NAD(P)H quinone dehydrogenase 1; an-ti-inflammatory pathways
Online: 7 May 2021 (09:38:38 CEST)
Background: Fullerenes and metallofullerenes can be considered promising nanopharmaceuticals themselves and as a basis for chemical modification. As reactive oxygen species homeostasis plays a vital role in cells, the study of their effect on genes involved in oxidative stress and anti-inflammatory response is of particular importance. Methods: Human fetal lung fibroblasts were incubated with aqueous dispersions of C60, C70, and Gd@C82 in concentrations of 5 nM and 1.5 µM for 1, 3, 24, and 72 hours. Cell viability, intracellular ROS, NOX4, NFκB, PRAR-γ, NRF2, heme oxygenase 1, and NAD(P)H quinone dehydrogenase 1 expression have been studied. Results & conclusion: The aqueous dispersions of C60, C70, and Gd@C82 fullerenes are active participants in ROS homeostasis. Low and high concentrations of AFDs have similar effects. C70 was the most inert substance, C60 was the most active substance. All AFDs have both a “prooxidant” and “antioxidant” effect, but with a different balance. Gd@C82 was a substance with more pronounced antioxidant and anti-inflammatory properties, while C70 had more pronounced “prooxidant” properties.
REVIEW | doi:10.20944/preprints202101.0626.v1
Subject: Biology, Anatomy & Morphology Keywords: BTB and CNC homology 1 BACH1; mitochondrial metabolism; glycolysis; heme oxygenase 1 (HMOX1); mitochondrial electron transport chain (ETC); Nrf2 (encoded by Nfe2l2); metformin; hemin; breast cancer; lung cancer
Online: 29 January 2021 (13:57:41 CET)
BTB domain and CNC homology 1 (BACH1) is a highly expressed transcription factor in tumors including breast and lung, relative to their non-tumor tissues. BACH1 is known to regulate multiple physiological processes including heme homeostasis, oxidative stress response, senescence, cell cycle, and mitosis. In a tumor, BACH1 promotes invasion and metastasis of cancer cells, and the expression of BACH1 presents a poor outcome for cancer patients including breast cancer patients. Recent studies identified novel functional roles of BACH1 in the regulation of metabolic pathways in cancer cells. BACH1 inhibits mitochondrial metabolism through transcriptional suppression of mitochondrial membrane genes. In addition, BACH1 suppresses activity of pyruvate dehydrogenase (PDH), a key enzyme that converts pyruvate to acetyl-CoA for the citric acid (TCA) cycle through transcriptional activation of pyruvate dehydrogenase kinase (PDK). Moreover, BACH1 increases glucose uptake and lactate secretion in aerobic glycolysis through the expression of metabolic enzymes involved such as hexokinase 2 (HK2) and glyceraldehyde 3- phosphate dehydrogenase (GAPDH). Pharmacological or genetic inhibition of BACH1 could reprogramme metabolic pathways, subsequently rendering metabolic vulnerability of cancer cells. Furthermore, inhibition of BACH1 decreased antioxidant-induced glycolysis rates as well as reduced migration and invasion of cancer cells, suggesting BACH1 as a potentially useful cancer therapeutic target.