Reactive Oxygen and Nitrogen Species–Induced Protein Modifications: Implication in Carcinogenesis and Anticancer Therapy

Cancer Research, Год журнала: 2018, Номер 78(21), С. 6040 - 6047

Опубликована: Окт. 17, 2018

Abstract Cancer is a complex disorder extremely dependent on its microenvironment and highly regulated by multiple intracellular extracellular stimuli. Studies show that reactive oxygen nitrogen species (RONS) play key roles in cancer initiation progression. Accumulation of RONS caused imbalance between generation activity antioxidant system (AOS) has been observed many types. This leads to alterations gene expression levels, signal transduction pathways, protein quality control machinery, is, processes regulate cell proliferation, migration, invasion, apoptosis. review focuses the latest advancements evidencing RONS-induced modifications redox-sensitive residues regulatory proteins, cysteine oxidation/S-sulfenylation/S-glutathionylation/S-nitrosylation tyrosine nitration, represent important molecular mechanisms underlying carcinogenesis. The oxidative/nitrosative cause activities effectors MAPK- PI3K/Akt-mediated signaling transcription factors (Nrf2, AP-1, NFκB, STAT3, p53), components ubiquitin/proteasomal autophagy/lysosomal degradation systems, chaperones, cytoskeletal proteins. Redox-sensitive RONS-generating enzymes, AOS can serve as targets for relevant anticancer drugs. Chemotherapeutic agents exert their action via induction apoptosis, while drug resistance associates with survival; this exploited selective therapy strategies. Res; 78(21); 6040–7. ©2018 AACR.

Язык: Английский

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Metabolic Heterogeneity of Cancer Cells: An Interplay between HIF-1, GLUTs, and AMPK

Cancers, Год журнала: 2020, Номер 12(4), С. 862 - 862

Опубликована: Апрель 2, 2020

It has been long recognized that cancer cells reprogram their metabolism under hypoxia conditions due to a shift from oxidative phosphorylation (OXPHOS) glycolysis in order meet elevated requirements energy and nutrients for proliferation, migration, survival. However, data accumulated over recent years increasingly provided evidence can revert OXPHOS maintain both reprogrammed metabolism, even the same tumor. This phenomenon, denoted as cell metabolic plasticity or hybrid depends on tumor micro-environment is highly heterogeneous influenced by an intensity of vasculature blood flow, oxygen concentration, nutrient supply, requires regulatory interplay between multiple oncogenes, transcription factors, growth reactive species (ROS), among others. Hypoxia-inducible factor-1 (HIF-1) AMP-activated protein kinase (AMPK) represent key modulators switch metabolism. The present review focuses cross-talks HIF-1, glucose transporters (GLUTs), AMPK with other proteins including oncogenes such c-Myc, p53, KRAS; factor-initiated B (PKB)/Akt, phosphatidyl-3-kinase (PI3K), mTOR signaling pathways; suppressors liver B1 (LKB1) TSC1 controlling switches pathways underlie chemo-resistance conventional anti-cancer therapy should be taken into account choosing molecular targets discover novel drugs.

Язык: Английский

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Redox Regulation of STAT1 and STAT3 Signaling

International Journal of Molecular Sciences, Год журнала: 2020, Номер 21(19), С. 7034 - 7034

Опубликована: Сен. 24, 2020

STAT1 and STAT3 are nuclear transcription factors that regulate genes involved in cell cycle, survival immune response. The cross-talk between these signaling pathways determines how cells integrate the environmental signals received ultimately translating them transcriptional regulation of specific sets genes. Despite being activated downstream common cytokine growth factors, play essentially antagonistic roles disruption their balance directs from to apoptotic death or inflammatory anti-inflammatory responses. Different mechanisms proposed explain this yin-yang relationship. Considering redox aspect STATs proteins, review attempts summarize current knowledge focusing attention on post-translational modifications affect activity.

Язык: Английский

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Carvacrol suppresses LPS-induced pro-inflammatory activation in RAW 264.7 macrophages through ERK1/2 and NF-kB pathway

International Immunopharmacology, Год журнала: 2019, Номер 75, С. 105743 - 105743

Опубликована: Июль 26, 2019

Язык: Английский

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Oxidative Stress, Kinase Activity and Inflammatory Implications in Right Ventricular Hypertrophy and Heart Failure under Hypobaric Hypoxia

International Journal of Molecular Sciences, Год журнала: 2020, Номер 21(17), С. 6421 - 6421

Опубликована: Сен. 3, 2020

High altitude (hypobaric hypoxia) triggers several mechanisms to compensate for the decrease in oxygen bioavailability. One of them is pulmonary artery vasoconstriction and its subsequent arterial remodeling. These changes can lead hypertension development right ventricular hypertrophy (RVH), heart failure (RHF) and, ultimately death. The aim this review describe most recent molecular pathways involved above conditions under type hypobaric hypoxia, including oxidative stress, inflammation, protein kinases activation fibrosis, current therapeutic approaches these conditions. This also includes knowledge long-term chronic intermittent hypoxia. Furthermore, highlights signaling related stress (Nox-derived O2.- H2O2), kinase (ERK5, p38α PKCα) activation, inflammatory molecules (IL-1β, IL-6, TNF-α NF-kB) hypoxia condition (HIF-1α). On other hand, have focused on abolishing hypoxia-induced RVH RHF via attenuation MCP-1, SDF-1 CXCR-4) through phytotherapy pharmacological trials. Nevertheless, further studies are necessary.

Язык: Английский

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