Reactive oxygen species (ROS) as pleiotropic physiological signalling agents

Nature Reviews Molecular Cell Biology, Journal Year: 2020, Volume and Issue: 21(7), P. 363 - 383

Published: March 30, 2020

Language: Английский

---

ROS in cancer therapy: the bright side of the moon

Experimental & Molecular Medicine, Journal Year: 2020, Volume and Issue: 52(2), P. 192 - 203

Published: Feb. 1, 2020

Abstract Reactive oxygen species (ROS) constitute a group of highly reactive molecules that have evolved as regulators important signaling pathways. It is now well accepted moderate levels ROS are required for several cellular functions, including gene expression. The production elevated in tumor cells consequence increased metabolic rate, mutation and relative hypoxia, excess quenched by antioxidant enzymatic nonenzymatic pathways the same cells. Moderate increases contribute to pathologic conditions, among which promotion progression, they involved different induce DNA mutation. However, also able trigger programmed cell death (PCD). Our review will emphasize molecular mechanisms useful development therapeutic strategies based on modulating treat cancer. Specifically, we report growing data highlight role generated Trojan horses eliminate cancer

Language: Английский

---

Superoxide dismutases: Dual roles in controlling ROS damage and regulating ROS signaling

The Journal of Cell Biology, Journal Year: 2018, Volume and Issue: 217(6), P. 1915 - 1928

Published: April 18, 2018

Superoxide dismutases (SODs) are universal enzymes of organisms that live in the presence oxygen. They catalyze conversion superoxide into oxygen and hydrogen peroxide. anions intended product dedicated signaling as well byproduct several metabolic processes including mitochondrial respiration. Through their activity, SOD control levels a variety reactive species (ROS) nitrogen species, thus both limiting potential toxicity these molecules controlling broad aspects cellular life regulated by functions. All aerobic have multiple proteins targeted to different subcellular locations, reflecting slow diffusion sources substrate superoxide. This compartmentalization also points need for fine local ROS possibility signal between compartments. In this review, we discuss studies model humans, which reveal dual roles damage regulating signaling.

Language: Английский

---

ROS signalling in the biology of cancer

Seminars in Cell and Developmental Biology, Journal Year: 2017, Volume and Issue: 80, P. 50 - 64

Published: June 4, 2017

Language: Английский

---

ROS Generation and Antioxidant Defense Systems in Normal and Malignant Cells

Oxidative Medicine and Cellular Longevity, Journal Year: 2019, Volume and Issue: 2019, P. 1 - 17

Published: Aug. 5, 2019

Reactive oxygen species (ROS) are by-products of normal cell activity. They produced in many cellular compartments and play a major role signaling pathways. Overproduction ROS is associated with the development various human diseases (including cancer, cardiovascular, neurodegenerative, metabolic disorders), inflammation, aging. Tumors continuously generate at increased levels that have dual their development. Oxidative stress can promote tumor initiation, progression, resistance to therapy through DNA damage, leading accumulation mutations genome instability, as well reprogramming metabolism signaling. On contrary, elevated induce death. This review covers current data on mechanisms generation existing antioxidant systems balancing redox state mammalian cells also be related tumors.

Language: Английский

---

ROS signaling under metabolic stress: cross-talk between AMPK and AKT pathway

Molecular Cancer, Journal Year: 2017, Volume and Issue: 16(1)

Published: April 13, 2017

Cancer cells are frequently confronted with metabolic stress in tumor microenvironments due to their rapid growth and limited nutrient supply. Metabolic induces cell death through ROS-induced apoptosis. However, cancer can adapt it by altering the pathways. AMPK AKT two primary effectors response stress: acts as an energy-sensing factor which rewires metabolism maintains redox balance. broadly promotes energy production abundance milieu, but role of under is dispute. Recent studies show that display antagonistic roles stress. stress-induced ROS signaling lies hub between reprogramming homeostasis. Here, we highlight cross-talk regulation on elimination, summarizes mechanism adaptability suggests potential options for therapeutics.

Language: Английский

---

Transcription Factor NRF2 as a Therapeutic Target for Chronic Diseases: A Systems Medicine Approach

Pharmacological Reviews, Journal Year: 2018, Volume and Issue: 70(2), P. 348 - 383

Published: March 5, 2018

Systems medicine has a mechanism-based rather than symptom- or organ-based approach to disease and identifies therapeutic targets in nonhypothesis-driven manner. In this work, we apply transcription factor nuclear (erythroid-derived 2)–like 2 (NRF2) by cross-validating its position protein–protein interaction network (the NRF2 interactome) functionally linked cytoprotection low-grade stress, chronic inflammation, metabolic alterations, reactive oxygen species formation. Multiscale analysis of these molecular profiles suggests alterations expression activity as common mechanism subnetwork diseases diseasome). This joins apparently heterogeneous phenotypes such autoimmune, respiratory, digestive, cardiovascular, metabolic, neurodegenerative diseases, along with cancer. Importantly, matches confirms silico several applications for NRF2-modulating drugs validated vivo at different phases clinical development. Pharmacologically, their profile is diverse electrophilic dimethyl fumarate, synthetic triterpenoids like bardoxolone methyl sulforaphane, DNA–protein inhibitors, even registered metformin statins, which activate may be repurposed indications within the cluster phenotypes. Thus, represents one first fully embraced classic systems approaches facilitate both drug development repurposing focusing on set that appear mechanistically linked. The resulting drugome therefore rapidly advance surprising options subset diseases.

Language: Английский

---

Engineering nanomedicine for glutathione depletion-augmented cancer therapy

Chemical Society Reviews, Journal Year: 2021, Volume and Issue: 50(10), P. 6013 - 6041

Published: Jan. 1, 2021

In this review, we systematically survey the most recent progress in engineering nanomedicine for intracellular glutathione consumption-augmented cancer therapy.

Language: Английский

---

Lipids and cancer: Emerging roles in pathogenesis, diagnosis and therapeutic intervention

Advanced Drug Delivery Reviews, Journal Year: 2020, Volume and Issue: 159, P. 245 - 293

Published: Jan. 1, 2020

With the advent of effective tools to study lipids, including mass spectrometry-based lipidomics, lipids are emerging as central players in cancer biology. Lipids function essential building blocks for membranes, serve fuel drive energy-demanding processes and play a key role signaling molecules regulators numerous cellular functions. Not unexpectedly, cells, well other cell types tumor microenvironment, exploit various ways acquire extensively rewire their metabolism part plastic context-dependent metabolic reprogramming that is driven by both oncogenic environmental cues. The resulting changes fate composition help cells thrive changing microenvironment supporting functions hallmarks, energetics, promoting feedforward signaling, resisting oxidative stresses, regulating intercellular communication immune responses. Supported close connection between altered lipid pathogenic process, specific profiles unique disease biomarkers, with diagnostic, prognostic predictive potential. Multiple preclinical studies illustrate translational promise exploiting cancer, critically, have shown context dependent actionable vulnerabilities can be rationally targeted, particularly combinatorial approaches. Moreover, themselves used membrane disrupting agents or components nanocarriers therapeutics. number compounds strategies approaching clinical trials, we at doorstep hitherto underappreciated hallmark promising target oncologist's strategy combat cancer.

Language: Английский

---

Cancer Metabolism: Phenotype, Signaling and Therapeutic Targets

Cells, Journal Year: 2020, Volume and Issue: 9(10), P. 2308 - 2308

Published: Oct. 16, 2020

Aberrant metabolism is a major hallmark of cancer. Abnormal cancer metabolism, such as aerobic glycolysis and increased anabolic pathways, has important roles in tumorigenesis, metastasis, drug resistance, stem cells. Well-known oncogenic signaling phosphoinositide 3-kinase (PI3K)/AKT, Myc, Hippo pathway, mediate metabolic gene expression increase enzyme activities. Vice versa, deregulated pathways contribute to defects cellular signal transduction which turn provide energy, building blocks, redox potentials for unrestrained cell proliferation. Studies clinical trials are being performed that focus on the inhibition enzymes by small molecules or dietary interventions (e.g., fasting, calorie restriction, intermittent fasting). Similar genetic heterogeneity, phenotypes cancers highly heterogeneous. This heterogeneity results from diverse cues tumor microenvironment mutations. Hence, overcoming plasticity an goal modern therapeutics. review highlights recent findings elucidates interactions between pathways. We also novel rationales designing next-generation drugs.

Language: Английский

---