Role of Reactive Oxygen Species in Cancer Progression: Molecular Mechanisms and Recent Advancements

Biomolecules, Journal Year: 2019, Volume and Issue: 9(11), P. 735 - 735

Published: Nov. 13, 2019

Reactive oxygen species (ROS) play a pivotal role in biological processes and continuous ROS production normal cells is controlled by the appropriate regulation between silver lining of low high concentration mediated effects. Interestingly, also dynamically influences tumor microenvironment known to initiate cancer angiogenesis, metastasis, survival at different concentrations. At moderate concentration, activates cell signaling cascade involving mitogen-activated protein kinase/extracellular signal-regulated kinases 1/2 (MAPK/ERK1/2), p38, c-Jun N-terminal kinase (JNK), phosphoinositide-3-kinase/ B (PI3K/Akt), which turn activate nuclear factor kappa-light-chain-enhancer activated (NF-κB), matrix metalloproteinases (MMPs), vascular endothelial growth (VEGF). concentrations, can cause apoptosis. Hence, it critically depends upon levels, either augment tumorigenesis or lead The major issue targeting dual actions effectively with respect bias, needs be monitored carefully impede angiogenesis metastasis for serve as potential therapeutic targets exogenously/endogenously. Overall, additional research required comprehend an effective anti-tumor modality target treating malignancies.

Language: Английский

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Modulating ROS to overcome multidrug resistance in cancer

Drug Resistance Updates, Journal Year: 2018, Volume and Issue: 41, P. 1 - 25

Published: Nov. 1, 2018

Language: Английский

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Toward Multi-Targeted Platinum and Ruthenium Drugs—A New Paradigm in Cancer Drug Treatment Regimens?

Chemical Reviews, Journal Year: 2019, Volume and Issue: 119(2), P. 1058 - 1137

Published: Jan. 14, 2019

While medicinal inorganic chemistry has been practised for over 5000 years, it was not until the late 1800s when Alfred Werner published his ground-breaking research on coordination that we began to truly understand nature of bond and structures stereochemistries metal complexes. We can now readily manipulate fine-tune their properties. This had led a multitude complexes with wide-ranging biomedical applications. review will focus use potential as important therapeutic agents treatment cancer. With major advances in technologies deeper understanding human genome, are strong position more fully carcinogenesis at molecular level. also rationally design develop drug molecules either selectively enhance or disrupt key biological processes and, doing so, optimize potential. heralded new era which moving from single- toward multitargeted approach. approach lies very heart chemistry. In this review, have endeavored showcase how "multitargeted" families metallodrugs may only reduce systemic toxicities associated modern day chemotherapeutics but address resistance issues plaguing many chemotherapeutic regimens. focused our attention incorporating platinum ruthenium ions given containing these already clinical advanced trials anticancer agents. The described herein target DNA contain vectors enable them cancer cells and/or moieties enzymes, peptides, intracellular proteins. Multitargeted designed mitochondria inspired by natural product activity described. A summary field past decade so be provided.

Language: Английский

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Platinum-based drugs for cancer therapy and anti-tumor strategies

Theranostics, Journal Year: 2022, Volume and Issue: 12(5), P. 2115 - 2132

Published: Jan. 1, 2022

Platinum-based drugs cisplatin, carboplatin, and oxaliplatin are widely used for chemotherapeutic eradication of cancer.However, the side effects platinum drugs, such as lack selectivity, high systemic toxicity, drug resistance, seriously limit their clinical application.With advancements in nanotechnology chemical synthesis, Pt-based anti-cancer have made great progress cancer therapy recent years.Many strategies relied on mechanism similar to cisplatin achieved some success by modifying existing drugs.Pt-based nanodrugs, nanoclusters, novel mechanisms potential tumor-targeted shown promising results application.In this review, we systematically explored development first-line chemotherapy clinic mechanisms.We also summarize application therapy, emphasizing modification enhance anti-tumor effect.Finally, address challenges faced especially Pt nanocluster-based treatment.The new targeted modifications undoubtedly provide a prospect improving current treatments.

Language: Английский

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Reactive Oxygen Species and Mitochondrial Dynamics: The Yin and Yang of Mitochondrial Dysfunction and Cancer Progression

Antioxidants, Journal Year: 2018, Volume and Issue: 7(1), P. 13 - 13

Published: Jan. 16, 2018

Mitochondria are organelles with a highly dynamic ultrastructure maintained by delicate equilibrium between its fission and fusion rates. Understanding the factors influencing this balance is important as perturbations to mitochondrial dynamics can result in pathological states. As terminal site of nutrient oxidation for cell, powerhouses harness energy form ATP process driven electron transport chain. Contemporaneously, electrons translocated within chain undergo spontaneous side reactions oxygen, giving rise superoxide variety other downstream reactive oxygen species (ROS). Mitochondrially-derived ROS mediate redox signaling or, excess, cause cell injury even death. Recent evidence suggests that tightly coupled generation depending on physiological status cell. Yet, mechanism which changes shape modulate function homeostasis less clear. Aberrant morphology may lead enhanced formation, which, turn, deteriorate health further exacerbate oxidative stress self-perpetuating vicious cycle. Here, we review latest findings intricate relationship production, focusing mainly role malignant disease.

Language: Английский

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The recent progress on metal–organic frameworks for phototherapy

Chemical Society Reviews, Journal Year: 2021, Volume and Issue: 50(8), P. 5086 - 5125

Published: Jan. 1, 2021

Some infectious or malignant diseases such as cancers are seriously threatening the health of human beings all over world. The commonly used antibiotic therapy cannot effectively treat these within a short time, and also bring about adverse effects drug resistance immune system damage during long-term systemic treatment. Phototherapy is an emerging antibiotic-free strategy to diseases. Upon light irradiation, phototherapeutic agents can generate cytotoxic reactive oxygen species (ROS) induce temperature increase, which leads death targeted cells. These two kinds killing strategies referred photodynamic (PDT) photothermal (PTT), respectively. So far, many photo-responsive have been developed. Among them, metal-organic framework (MOF) becoming one most promising materials because its structure chemical compositions be easily modulated achieve specific functions. MOFs intrinsic ability under rational design MOF construction, serve carrier therapeutic agents, owing tunable porosity. provide feasibility for various combined therapies targeting methods, improves efficiency phototherapy. In this review, we firstly investigated principles phototherapy, comprehensively summarized recent advances in PDT, PTT synergistic therapy, from construction modification. We expect that our demonstration will shed on future development field, it step closer clinical trials.

Language: Английский

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Restraining Cancer Cells by Dual Metabolic Inhibition with a Mitochondrion‐Targeted Platinum(II) Complex

Angewandte Chemie International Edition, Journal Year: 2019, Volume and Issue: 58(14), P. 4638 - 4643

Published: Jan. 29, 2019

Abstract Cancer cells usually adapt metabolic phenotypes to chemotherapeutics. A defensive strategy against this flexibility is modulate signaling pathways relevant cancer bioenergetics. triphenylphosphonium‐modified terpyridine platinum(II) complex (TTP) was designed inhibit thioredoxin reductase (TrxR) and multiple metabolisms of cells. TTP exhibited enhanced cytotoxicity cisplatin‐insensitive human ovarian in a caspase‐3‐independent manner showed preferential inhibition mitochondrial TrxR. The morphology function mitochondria were severely damaged, the levels cellular reactive oxygen species decreased. As result, exerted strong both glycolytic bioenergetics, thus inducing enter hypometabolic state.

Language: Английский

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Targeting the Thioredoxin System as a Strategy for Cancer Therapy

Journal of Medicinal Chemistry, Journal Year: 2019, Volume and Issue: 62(16), P. 7309 - 7321

Published: April 9, 2019

Thioredoxin reductase (TrxR) participates in the regulation of redox reactions organisms. It works mainly via its substrate molecule, thioredoxin, to maintain balance and regulate signal transduction, which controls cell proliferation, differentiation, death, other important physiological processes. In recent years, increasing evidence has shown that overactivation TrxR is related development tumors. The exploration TrxR-targeted antitumor drugs attracted wide attention expected provide new therapies for cancer treatment. this perspective, we highlight specific relationship between apoptotic signaling pathways. cytoplasm mitochondria both contain TrxR, resulting activation apoptosis. activity influences reactive oxygen species (ROS) further regulates inflammatory pathway. addition, discuss representative inhibitors with anticancer analyze challenges developing as drugs.

Language: Английский

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Small molecules regulating reactive oxygen species homeostasis for cancer therapy

Medicinal Research Reviews, Journal Year: 2020, Volume and Issue: 41(1), P. 342 - 394

Published: Sept. 27, 2020

Elevated intracellular reactive oxygen species (ROS) and antioxidant defense systems have been recognized as one of the hallmarks cancer cells. Compared with normal cells, cells exhibit increased ROS to maintain their malignant phenotypes are more dependent on "redox adaptation" mechanism. Thus, there two apparently contradictory but virtually complementary therapeutic strategies for regulation prevent or treat cancer. The first strategy, that is, chemoprevention, is reduce either by suppressing production pathways employing antioxidants enhance clearance, which protects from transformation inhibits early stage tumorigenesis. second strategy ROS-mediated anticancer therapy, stimulates a toxicity threshold activate ROS-induced cell death pathways. Therefore, targeting ROS-related small-molecule candidates considered be promising treatment tumors. We herein briefly introduce source ROS, then focus small molecules regulate show efficacy in therapy perspective pharmacophores. Finally, we discuss several challenges developing agents based propose direction future development.

Language: Английский

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Recent advances on modulation of H2O2 in tumor microenvironment for enhanced cancer therapeutic efficacy

Coordination Chemistry Reviews, Journal Year: 2023, Volume and Issue: 481, P. 215049 - 215049

Published: Feb. 9, 2023

Language: Английский

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