Understanding mechanisms of antioxidant action in health and disease

Nature Reviews Molecular Cell Biology, Год журнала: 2023, Номер 25(1), С. 13 - 33

Опубликована: Сен. 15, 2023

Язык: Английский

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Hyperglycemia and Oxidative Stress: An Integral, Updated and Critical Overview of Their Metabolic Interconnections

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(11), С. 9352 - 9352

Опубликована: Май 27, 2023

This review focuses on the multiple and reciprocal relationships that exist between oxidative stress, hyperglycemia diabetes related metabolic disorders. Human metabolism uses most of consumed glucose under aerobic conditions. Oxygen is needed in mitochondria to obtain energy, as well for action microsomal oxidases cytosolic pro-oxidant enzymes. relentlessly generates a certain amount reactive oxygen species (ROS). Although ROS are intracellular signals necessary some physiological processes, their accumulation leads hyperglycemia, progressive resistance insulin. A cellular versus an antioxidant equilibrium would regulate levels, but pro-inflammatory conditions feed back each other relevance interconnections tends increase those Hyperglycemia promotes collateral through protein kinase C, polyols hexosamine routes. In addition, it also facilitates spontaneous auto-oxidation formation advanced glycation end products (AGEs), which turn interact with receptors (RAGE). The mentioned processes undermine structures, finally giving place progressively greater degree stress further alterations, complications. NFκB major transcription factor involved expression mediators, while Nrf2 regulating response. FoxO equilibrium, its role controversial. summarizes key factors linking diverse routes enhanced vice versa, emphasizing desirable balance proteins.

Язык: Английский

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Suppression of Spry1 reduces HIF1α-dependent glycolysis and impairs angiogenesis in BRAF-mutant cutaneous melanoma

Journal of Experimental & Clinical Cancer Research, Год журнала: 2025, Номер 44(1)

Опубликована: Фев. 14, 2025

About 50% of cutaneous melanoma (CM) harbors the activating BRAFV600 mutation which exerts most oncogenic effects through MAPK signaling pathway. In last years, a number modulators have been identified, including Spry1. this context, we recently demonstrated that knockout Spry1 (Spry1KO) in BRAFV600-mutant CM led to cell cycle arrest and apoptosis, repressed proliferation vitro, reduced tumor growth vivo. Despite these findings, however, precise molecular mechanism linking remains be elucidated. Immunoprecipitation coupled mass spectrometry was employed gain insight into interactome. gene knocked-out using CRISPR strategy BRAF-mutant lines. Transmission electron microscopy used assess relationship between expression mitochondrial morphology. By vitro vivo models, Spry1KO were investigated RNA-sequencing, quantitative real-time PCR, Western blot, immunofluorescence analyses. The Seahorse XF24 assay allowed measurement cellular metabolism our model. Angiogenic potential assessed tube formation assays CD31 staining. mainly located mitochondria cells where it interacted with key molecules involved homeostasis. loss resulted shape alterations dysfunction, associated increased reactive oxygen species production. agreement, found nuclear hypoxia-inducible factor-1 alpha (HIF1α) protein levels clones both along its glycolysis related genes. Accordingly, Ingenuity Pathway Analysis identified "HIF1α Signaling" as significant function affected by silencing, whereas glycolytic significantly impaired depleted cells. addition, results indicated vascular endothelial factor A down-regulated following Spry1KO, possibly result dysfunction. Consistently, observed substantial impairment angiogenesis, staining Altogether, findings identify regulator homeostasis, uncover previously unrecognized role for regulating HIF1α angiogenesis CM. profoundly impacts on while concomitantly impairing HIF1α-dependent reducing cells, thus providing therapeutic target improve treatment.

Язык: Английский

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Nrf2 signaling pathway: current status and potential therapeutic targetable role in human cancers

Frontiers in Oncology, Год журнала: 2023, Номер 13

Опубликована: Сен. 22, 2023

Cancer is a borderless global health challenge that continues to threaten human health. Studies have found oxidative stress (OS) often associated with the etiology of many diseases, especially aging process and cancer. Involved in OS reaction as key transcription factor, Nrf2 pivotal regulator cellular redox state detoxification. can prevent damage by regulating gene expression antioxidant response elements (ARE) promote process. generated an imbalance promotes accumulation mutations genome instability, thus establishment development different cancers. activation regulates plethora processes inducing proliferation, differentiation death, strongly OS-mediated What’s more, also involved anti-inflammatory effects metabolic disorders, neurodegenerative multidrug resistance. highly expressed multiple body parts digestive system, respiratory reproductive system nervous system. In oncology research, has emerged promising therapeutic target. Therefore, certain natural compounds drugs exert anti-cancer through signaling pathway, blocking pathway reduce some types tumor recurrence rates increase sensitivity chemotherapy. However, Nrf2’s dual role controversial impact cancer are inevitable consideration factors when treating this review, we summarized current biological characteristics its mechanism cells, discussed Keap1/Nrf2/ARE downstream genes, elaborated related pathways such AMPK/mTOR NF-κB. Besides, main target strategies using inhibitors or activators, well possible positive negative were reviewed. It be concluded serves important factor formation development, provides basis for targeted therapy

Язык: Английский

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Baicalin and baicalein in modulating tumor microenvironment for cancer treatment: A comprehensive review with future perspectives

Pharmacological Research, Год журнала: 2023, Номер 199, С. 107032 - 107032

Опубликована: Дек. 5, 2023

Cancer is a leading cause of death worldwide. The burden cancer incidence and mortality increasing rapidly. New approaches to prevention treatment are urgently needed. Natural products reliable powerful sources for anticancer drug discovery. Baicalin baicalein, two major flavones isolated from Scutellaria baicalensis Georgi, multi-purpose traditional medicinal plant in China, exhibit activities against multiple cancers. Of note, these phytochemicals extremely low toxicity normal cells. Besides their cytotoxic cytostatic toward diverse tumor cells, recent studies demonstrated that baicalin baicalein modulate variety stromal cells extracellular matrix (ECM) the microenvironment (TME), which essential tumorigenesis, progression metastasis. In this review, we summarize therapeutic potential mechanism action regulation microenvironmental immune endothelial fibroblasts, ECM reshape TME signaling, inhibition angiogenesis, progression, addition, discuss biotransformation pathways related challenges future research directions improve bioavailability clinical applications. Recent advances warrant continued study as important natural ways interception therapy.

Язык: Английский

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Green synthesis of copper oxide nanoparticles using walnut shell and their size dependent anticancer effects on breast and colorectal cancer cell lines

Scientific Reports, Год журнала: 2024, Номер 14(1)

Опубликована: Сен. 2, 2024

Abstract Metal oxide nanoparticles(NPs) contain unique properties which have made them attractive agents in cancer treatment. The CuO nanoparticles were green synthesized using walnut shell powder different calcination temperatures (400°, 500°, 700°, and 900 °C). are characterized by FTIR, XRD, BET, SEM DLS analyses. analyses showed that increasing the required temperature for synthesizing NPs, their size was increased. DPPH analysis displayed no significant anti-oxidative of NPs. MTT all NPs exhibited cytotoxic effects on MCF-7, HCT-116, HEK-293 cell lines. Among CuO-900 least effect line (IC 50 = 330.8 µg/ml). Hoechst staining real-time suggested induced apoptosis elevation p53 Bax genes expression levels. Also, increased Nrf-2 gene level MCF-7 cells, despite HCT-116 cells. As can be concluded from results, exerted promising breast colon

Язык: Английский

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Maackiain induces apoptosis and autophagy via ROS-mediated endoplasmic reticulum stress in endometrial cancer

International Immunopharmacology, Год журнала: 2025, Номер 147, С. 113935 - 113935

Опубликована: Янв. 5, 2025

Язык: Английский

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Complex II ambiguities—FADH2 in the electron transfer system

Journal of Biological Chemistry, Год журнала: 2023, Номер 300(1), С. 105470 - 105470

Опубликована: Ноя. 22, 2023

The prevailing notion that reduced cofactors NADH and FADH

Язык: Английский

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A state-of-the-art review on the NRF2 in Hepatitis virus-associated liver cancer

Cell Communication and Signaling, Год журнала: 2023, Номер 21(1)

Опубликована: Ноя. 9, 2023

Abstract According to a paper released and submitted WHO by IARC scientists, there would be 905,700 new cases of liver cancer diagnosed globally in 2020, with 830,200 deaths expected as direct result. Hepatitis B virus (HBV) hepatitis C (HCV), D (HDV) all play critical roles the pathogenesis hepatocellular carcinoma (HCC), despite rising prevalence HCC due non-infectious causes. Liver cirrhosis are devastating consequences HBV HCV infections, which widespread worldwide. Associated high mortality rate, these infections cause about 1.3 million annually primary globally. In addition causing insertional mutations viral gene integration, epigenetic alterations inducing chronic immunological dysfunction methods viruses turn hepatocytes into cancerous ones. While expanding our knowledge illness, identifying pathways also give possibilities for novel diagnostic treatment methods. Nuclear factor erythroid 2-related 2 (NRF2) activation is gaining popularity option oxidative stress (OS), inflammation, metabolic abnormalities. Numerous studies have shown that elevated Nrf2 expression linked HCC, providing more evidence HCC. This aberrant signaling drives cell proliferation, initiates angiogenesis invasion, imparts drug resistance. As result, this master regulator may promising target addition, common effect contributes pathogenesis, development, chronicity infection. However, certain suppress activity, helpful maintaining cellular homeostasis. paper, we discussed influence deregulation on life cycle associated HCV. We summed up mechanisms modulation deregulated viruses. Moreover, describe molecular mechanism modulated cancer, stem cells (LCSCs), caused

Язык: Английский

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Molecular Mechanisms of Oxidative Stress in Acute Kidney Injury: Targeting the Loci by Resveratrol

International Journal of Molecular Sciences, Год журнала: 2023, Номер 25(1), С. 3 - 3

Опубликована: Дек. 19, 2023

Reactive oxygen species are a group of cellular molecules that stand as double-edged swords, their good and bad being discriminated by precise balance. Several metabolic reactions in the biological system generate these interact with atoms to regulate functions ranging from cell homeostasis death. A prooxidative state concomitant decreased clearance such leads oxidative stress, which contributes prime pathophysiological mechanism various diseases including renal disorders, acute kidney injury. However, targeting generation stress disorders an antioxidant, resveratrol, is gaining considerable therapeutic importance known improve condition preclinical studies. This review aims discuss molecular mechanisms injury its amelioration resveratrol. The major sources data were PubMed Google Scholar, studies last five years primarily included, significant earlier also considered. Mitochondrial dysfunction, enzymatic reactions, protein misfolding reactive injury, interrupting loci or intersection other components resveratrol can mitigate severity condition.

Язык: Английский

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