Mitochondrial Dysfunction at the Center of Cancer Therapy.

Abstract:

: Significance: Mitochondria undergo constant morphological changes through fusion, fission, and mitophagy. As the key organelle in cells, mitochondria are responsible for numerous essential cellular functions such as metabolism, regulation of calcium (Ca2+), generation of reactive oxygen species, and initiation of apoptosis. Unsurprisingly, mitochondrial dysfunctions underlie many pathologies including cancer. Recent Advances: Currently, the gold standard for cancer treatment is chemotherapy, radiation, and surgery. However, the efficacy of these treatments varies across different cancer cells. It has been suggested that mitochondria may be at the center of these diverse responses. In the past decade, significant advances have been made in understanding distinct types of mitochondrial dysfunctions in cancer. Through investigations of underlying mechanisms, more effective treatment options are developed. Critical Issues: We summarize various mitochondria dysfunctions in cancer progression that have led to the development of therapeutic options. Current mitochondrial-targeted therapies and challenges are discussed. Future Directions: To address the "root" of cancer, utilization of mitochondrial-targeted therapy to target cancer stem cells may be valuable. Investigation of other areas such as mitochondrial trafficking may offer new insights into cancer therapy. Moreover, common antibiotics could be explored as mitocans, and synthetic lethality screens can be utilized to overcome the plasticity of cancer cells.

journal_name

Antioxid Redox Signal

authors

Chiu HY,Tay EXY,Ong DST,Taneja R

doi

10.1089/ars.2019.7898

subject

Has Abstract

pub_date

2020-02-10 00:00:00

pages

309-330

issue

5

eissn

1523-0864

issn

1557-7716

journal_volume

32

pub_type

杂志文章
  • Rho/Rho-associated coiled-coil forming kinase pathway as therapeutic targets for statins in atherosclerosis.

    abstract:SIGNIFICANCE:The 3-hydroxy-methylglutaryl coenzyme A reductase inhibitors or statins are important therapeutic agents for lowering serum cholesterol levels. However, recent studies suggest that statins may exert atheroprotective effects beyond cholesterol lowering. These so-called "pleiotropic effects" include effects ...

    journal_title:Antioxidants & redox signaling

    pub_type: 杂志文章,评审

    doi:10.1089/ars.2013.5524

    authors: Sawada N,Liao JK

    更新日期:2014-03-10 00:00:00

  • The free radical theory of aging.

    abstract::Aging is the accumulation of changes that increase the risk of death. Aging changes can be attributed to development, genetic defects, the environment, disease, and an inborn process: the aging process. The latter is the major risk factor for disease and death after age 28 in the developed countries. In these countrie...

    journal_title:Antioxidants & redox signaling

    pub_type: 杂志文章,评审

    doi:10.1089/152308603770310202

    authors: Harman D

    更新日期:2003-10-01 00:00:00

  • Apoptosis signaling kinases: from stress response to health outcomes.

    abstract::Apoptosis is a highly regulated process essential for the development and homeostasis of multicellular organisms. Whereas caspases, a large family of intracellular cysteine proteases, play central roles in the execution of apoptosis, other proapoptotic and antiapoptotic regulators such as the members of the Bcl-2 fami...

    journal_title:Antioxidants & redox signaling

    pub_type: 杂志文章,评审

    doi:10.1089/ars.2010.3392

    authors: Takeda K,Naguro I,Nishitoh H,Matsuzawa A,Ichijo H

    更新日期:2011-08-01 00:00:00

  • Reactive oxygen as modulator of TNF and fas receptor-mediated apoptosis in vivo: studies with glutathione peroxidase-deficient mice.

    abstract::Reactive oxygen species (ROS) can directly induce or enhance tumor necrosis factor (TNF)-mediated apoptosis in a number of different cell lines. To test the relevance of intracellular ROS in modulating apoptotic signaling in vivo, we evaluated hepatocellular apoptosis mediated by the TNF or Fas receptor in wild-type a...

    journal_title:Antioxidants & redox signaling

    pub_type: 杂志文章

    doi:10.1089/152308602760598873

    authors: Bajt ML,Ho YS,Vonderfecht SL,Jaeschke H

    更新日期:2002-10-01 00:00:00

  • Molecular targeting of proteins by L-homocysteine: mechanistic implications for vascular disease.

    abstract::Hyperhomocysteinemia is an independent risk factor for cardiovascular disease, complications of pregnancy, cognitive impairment, and osteoporosis. That elevated homocysteine leads to vascular dysfunction may be the linking factor between these apparently unrelated pathologies. Although a growing body of evidence sugge...

    journal_title:Antioxidants & redox signaling

    pub_type: 杂志文章,评审

    doi:10.1089/ars.2007.1809

    authors: Glushchenko AV,Jacobsen DW

    更新日期:2007-11-01 00:00:00

  • Free radicals in cross talk between autophagy and apoptosis.

    abstract:SIGNIFICANCE:Oxidative (reactive oxygen species [ROS]) and nitrosative (reactive nitrogen species [RNS]) stress affects many physiological processes, including survival and death. Although high levels of ROS/RNS mainly causes cell death, low levels of free radicals directly modulate the activities of transcriptional fa...

    journal_title:Antioxidants & redox signaling

    pub_type: 杂志文章,评审

    doi:10.1089/ars.2013.5746

    authors: Kaminskyy VO,Zhivotovsky B

    更新日期:2014-07-01 00:00:00

  • Mitochondria as Target for Tumor Management of Hemangioendothelioma.

    abstract:: Aims: Hemangioendothelioma (HE) may be benign or malignant. Mouse hemangioendothelioma endothelial (EOMA) cells are validated to study mechanisms in HE. This work demonstrates that EOMA cells heavily rely on mitochondria to thrive. Thus, a combination therapy, including we...

    journal_title:Antioxidants & redox signaling

    pub_type: 杂志文章

    doi:10.1089/ars.2020.8059

    authors: Gordillo GM,Biswas A,Singh K,Sen A,Guda PR,Miller C,Pan X,Khanna S,Cadenas E,Sen CK

    更新日期:2021-01-10 00:00:00

  • Reactive Oxygen Species and Mitochondrial Homeostasis as Regulators of Stem Cell Fate and Function.

    abstract:SIGNIFICANCE:The precise role and impact of reactive oxygen species (ROS) in stem cells, which are essential for lifelong tissue homeostasis and regeneration, remain of significant interest to the field. The long-term regenerative potential of a stem cell compartment is determined by the delicate balance between quiesc...

    journal_title:Antioxidants & redox signaling

    pub_type: 杂志文章,评审

    doi:10.1089/ars.2017.7273

    authors: Tan DQ,Suda T

    更新日期:2018-07-10 00:00:00

  • The Redox-Metabolic Couple of T Lymphocytes: Potential Consequences for Hypertension.

    abstract:: Significance: T lymphocytes, as part of the adaptive immune system, possess the ability to activate and function in extreme cellular microenvironments, which requires these cells to remain highly malleable. One mechanism in which T lymphocytes achieve this adaptability is ...

    journal_title:Antioxidants & redox signaling

    pub_type: 杂志文章

    doi:10.1089/ars.2020.8042

    authors: Moshfegh CM,Case AJ

    更新日期:2020-04-30 00:00:00

  • Oxygen sensing in the carotid body and its relation to heart failure.

    abstract::This brief review first touches on the origins of the earth's oxygen. It then identifies and locates the principal oxygen sensor in vertebrates, the carotid body (CB). The CB is unique in that in human subjects, it is the only sensor of lower than normal levels in the partial pressure of oxygen (hypoxia, HH). Another ...

    journal_title:Antioxidants & redox signaling

    pub_type: 杂志文章

    doi:10.1089/ars.2007.1546

    authors: Fitzgerald RS,Shirahata M,Balbir A,Grossman CE

    更新日期:2007-06-01 00:00:00

  • Plant polyphenols regulate chemokine expression and tissue repair in human keratinocytes through interaction with cytoplasmic and nuclear components of epidermal growth factor receptor system.

    abstract:AIMS:To evaluate mechanisms underlying modulation of inflammatory chemokines in primary human keratinocytes (normal human epidermal keratinocytes) and repair-related processes in wound models by plant polyphenols (PPs) with antioxidant and superoxide scavenging properties (verbascoside [Vb], resveratrol [Rv], polydatin...

    journal_title:Antioxidants & redox signaling

    pub_type: 杂志文章

    doi:10.1089/ars.2011.4053

    authors: Pastore S,Lulli D,Fidanza P,Potapovich AI,Kostyuk VA,De Luca C,Mikhal'chik E,Korkina LG

    更新日期:2012-02-15 00:00:00

  • Oxidative damage compromises energy metabolism in the axonal degeneration mouse model of X-adrenoleukodystrophy.

    abstract:AIMS:Chronic metabolic impairment and oxidative stress are associated with the pathogenesis of axonal dysfunction in a growing number of neurodegenerative conditions. To investigate the intertwining of both noxious factors, we have chosen the mouse model of adrenoleukodystrophy (X-ALD), which exhibits axonal degenerati...

    journal_title:Antioxidants & redox signaling

    pub_type: 杂志文章

    doi:10.1089/ars.2010.3877

    authors: Galino J,Ruiz M,Fourcade S,Schlüter A,López-Erauskin J,Guilera C,Jove M,Naudi A,García-Arumí E,Andreu AL,Starkov AA,Pamplona R,Ferrer I,Portero-Otin M,Pujol A

    更新日期:2011-10-15 00:00:00

  • Redox control of renal function and hypertension.

    abstract::Loss of redox homeostasis and formation of excessive free radicals play an important role in the pathogenesis of kidney disease and hypertension. Free radicals such as reactive oxygen species (ROS) are necessary in physiologic processes. However, loss of redox homeostasis contributes to proinflammatory and profibrotic...

    journal_title:Antioxidants & redox signaling

    pub_type: 杂志文章,评审

    doi:10.1089/ars.2008.2034

    authors: Nistala R,Whaley-Connell A,Sowers JR

    更新日期:2008-12-01 00:00:00

  • Endothelial Nanomechanics in the Context of Endothelial (Dys)function and Inflammation.

    abstract:SIGNIFICANCE:Stiffness of endothelial cells is closely linked to the function of the vasculature as it regulates the release of vasoactive substances such as nitric oxide (NO) and reactive oxygen species. The outer layer of endothelial cells, consisting of the glycocalyx above and the cortical zone beneath the plasma m...

    journal_title:Antioxidants & redox signaling

    pub_type: 杂志文章,评审

    doi:10.1089/ars.2017.7327

    authors: Fels J,Kusche-Vihrog K

    更新日期:2019-03-01 00:00:00

  • NADPH oxidase-mediated triggering of inflammasome activation in mouse podocytes and glomeruli during hyperhomocysteinemia.

    abstract:AIM:Our previous studies have shown that NOD-like receptor protein (NALP3) inflammasome activation is importantly involved in podocyte dysfunction and glomerular sclerosis induced by hyperhomocysteinemia (hHcys). The present study was designed to test whether nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-...

    journal_title:Antioxidants & redox signaling

    pub_type: 杂志文章

    doi:10.1089/ars.2012.4666

    authors: Abais JM,Zhang C,Xia M,Liu Q,Gehr TW,Boini KM,Li PL

    更新日期:2013-05-01 00:00:00

  • Neuronal apoptosis in neurodegeneration.

    abstract::Apoptosis mediates the precise and programmed natural death of neurons and is a physiologically important process in neurogenesis during maturation of the central nervous system. However, premature apoptosis and/or an aberration in apoptosis regulation is implicated in the pathogenesis of neurodegeneration, a multifac...

    journal_title:Antioxidants & redox signaling

    pub_type: 杂志文章,评审

    doi:10.1089/ars.2007.1511

    authors: Okouchi M,Ekshyyan O,Maracine M,Aw TY

    更新日期:2007-08-01 00:00:00

  • Forkhead box o as a sensor, mediator, and regulator of redox signaling.

    abstract::The forkhead box O (FOXO) family of transcription factors regulates a variety of cellular programs, including cell cycle arrest, reactive oxygen species (ROS) scavenging, and apoptosis, and are of key importance in the decision over cell fate. In animal model systems it has been shown that FOXO is involved in the regu...

    journal_title:Antioxidants & redox signaling

    pub_type: 杂志文章,评审

    doi:10.1089/ars.2010.3403

    authors: de Keizer PL,Burgering BM,Dansen TB

    更新日期:2011-03-15 00:00:00

  • Reduction-responsive polymeric micelles and vesicles for triggered intracellular drug release.

    abstract:SIGNIFICANCE:The therapeutic effects of current micellar and vesicular drug formulations are restricted by slow and inefficient drug release at the pathological site. The development of smart polymeric nanocarriers that release drugs upon arriving at the target site has received a tremendous amount of attention for can...

    journal_title:Antioxidants & redox signaling

    pub_type: 杂志文章,评审

    doi:10.1089/ars.2013.5733

    authors: Sun H,Meng F,Cheng R,Deng C,Zhong Z

    更新日期:2014-08-10 00:00:00

  • Tetrahydrobiopterin in cardiovascular health and disease.

    abstract::Tetrahydrobiopterin (BH4) functions as a cofactor for several important enzyme systems, and considerable evidence implicates BH4 as a key regulator of endothelial nitric oxide synthase (eNOS) in the setting of cardiovascular health and disease. BH4 bioavailability is determined by a balance of enzymatic de novo synthe...

    journal_title:Antioxidants & redox signaling

    pub_type: 杂志文章,评审

    doi:10.1089/ars.2013.5566

    authors: Bendall JK,Douglas G,McNeill E,Channon KM,Crabtree MJ

    更新日期:2014-06-20 00:00:00

  • Overexpression of mitochondrial ferritin sensitizes cells to oxidative stress via an iron-mediated mechanism.

    abstract::Mitochondrial ferritin (MtFt) is a newly identified H-ferritin-like protein expressed only in mitochondria. Previous studies have shown that its overexpression markedly affects intracellular iron homeostasis and rescues defects caused by frataxin deficiency. To assess how MtFt exerts its function under oxidative stres...

    journal_title:Antioxidants & redox signaling

    pub_type: 杂志文章

    doi:10.1089/ars.2008.2306

    authors: Lu Z,Nie G,Li Y,Soe-Lin S,Tao Y,Cao Y,Zhang Z,Liu N,Ponka P,Zhao B

    更新日期:2009-08-01 00:00:00

  • The Interplay Between Systemic Inflammation, Oxidative Stress, and Tissue Remodeling in Tuberculosis.

    abstract:: Significance: Excessive and prolonged proinflammatory responses are associated with oxidative stress, which is commonly observed during chronic tuberculosis (TB). Such condition favors tissue destruction and consequently bacterial spread. A tissue remodeling program is als...

    journal_title:Antioxidants & redox signaling

    pub_type: 杂志文章

    doi:10.1089/ars.2020.8124

    authors: Amaral EP,Vinhaes CL,Oliveira-de-Souza D,Nogueira B,Akrami KM,Andrade BB

    更新日期:2021-02-20 00:00:00

  • Aging exacerbates hydrogen peroxide-induced alteration of vascular reactivity in rats.

    abstract::Reactive oxygen species (ROS) such as superoxide anion (O2-*) and hydrogen peroxide (H2O2) can be produced by vascular endothelium and smooth muscle cells under diverse physiological and pathophysiological situations. These species are known to exert various deleterious effects by which they might induce changes in va...

    journal_title:Antioxidants & redox signaling

    pub_type: 杂志文章

    doi:10.1089/ars.2000.2.2-363

    authors: Tanguy S,Boucher F,Toufektsian MC,Besse S,de Leiris J

    更新日期:2000-07-01 00:00:00

  • Regulation of tumor necrosis factor-induced, mitochondria- and reactive oxygen species-dependent cell death by the electron flux through the electron transport chain complex I.

    abstract::Tumor necrosis factor (TNF) induces a caspase-independent but mitochondria-dependent cell death process in the mouse fibrosarcoma cell line L929. Mitochondria actively participate in this TNF-induced necrotic cell death by the generation of mitochondrial reactive oxygen species (ROS). The aim of this study was to iden...

    journal_title:Antioxidants & redox signaling

    pub_type: 杂志文章

    doi:10.1089/ars.1999.1.3-285

    authors: Goossens V,Stangé G,Moens K,Pipeleers D,Grooten J

    更新日期:1999-10-01 00:00:00

  • Nitrite and nitrite reductases: from molecular mechanisms to significance in human health and disease.

    abstract::Nitrite, previously considered physiologically irrelevant and a simple end product of endogenous nitric oxide (NO) metabolism, is now envisaged as a reservoir of NO to be activated in response to oxygen (O(2)) depletion. In the first part of this review, we summarize and compare the mechanisms of nitrite-dependent pro...

    journal_title:Antioxidants & redox signaling

    pub_type: 杂志文章,评审

    doi:10.1089/ars.2011.4196

    authors: Castiglione N,Rinaldo S,Giardina G,Stelitano V,Cutruzzolà F

    更新日期:2012-08-15 00:00:00

  • Detection of lipid radicals using EPR.

    abstract::Cells oxidize molecules to generate energy and to make the materials to build and support the structures and functions needed for life. However, unwanted oxidations can damage these same structures and impair function. Lipids (the lipids in membranes and lipoproteins) are targets of unwanted oxidations. The primary me...

    journal_title:Antioxidants & redox signaling

    pub_type: 杂志文章,评审

    doi:10.1089/152308604773934396

    authors: Venkataraman S,Schafer FQ,Buettner GR

    更新日期:2004-06-01 00:00:00

  • H₂O₂-Activated Mitochondrial Phospholipase iPLA₂γ Prevents Lipotoxic Oxidative Stress in Synergy with UCP2, Amplifies Signaling via G-Protein-Coupled Receptor GPR40, and Regulates Insulin Secretion in Pancreatic β-Cells.

    abstract:AIMS:Pancreatic β-cell chronic lipotoxicity evolves from acute free fatty acid (FA)-mediated oxidative stress, unprotected by antioxidant mechanisms. Since mitochondrial uncoupling protein-2 (UCP2) plays antioxidant and insulin-regulating roles in pancreatic β-cells, we tested our hypothesis, that UCP2-mediated uncoupl...

    journal_title:Antioxidants & redox signaling

    pub_type: 杂志文章

    doi:10.1089/ars.2014.6195

    authors: Ježek J,Dlasková A,Zelenka J,Jabůrek M,Ježek P

    更新日期:2015-10-20 00:00:00

  • Ascorbic Acid Route to the Endoplasmic Reticulum: Function and Role in Disease.

    abstract:: Significance: Humans cannot synthesize ascorbic acid (AscH2) (vitamin C), so deficiencies in dietary AscH2 cause the life-threatening disease of scurvy and many other diseases. After oral ingestion, plasma AscH2 concentrations are strictly controlled by transporters, which...

    journal_title:Antioxidants & redox signaling

    pub_type: 杂志文章

    doi:10.1089/ars.2019.7912

    authors: Pozzer D,Invernizzi RW,Blaauw B,Cantoni O,Zito E

    更新日期:2020-01-22 00:00:00

  • Potential mechanisms for the inhibition of tumor cell growth by manganese superoxide dismutase.

    abstract::Studies from many laboratories have shown that overexpression of manganese superoxide dismutase (MnSOD) inhibits the growth of numerous tumor cell types. The inhibition of tumor cell growth can be attributed to the increase in the steady-state levels of H2O2 as a result of the increased dismuting activity of MnSOD. He...

    journal_title:Antioxidants & redox signaling

    pub_type: 杂志文章

    doi:10.1089/15230860152409013

    authors: Kim KH,Rodriguez AM,Carrico PM,Melendez JA

    更新日期:2001-06-01 00:00:00

  • Britanin Ameliorates Cerebral Ischemia-Reperfusion Injury by Inducing the Nrf2 Protective Pathway.

    abstract:AIMS:Oxidative stress is considered the major cause of tissue injury after cerebral ischemia. The nuclear factor erythroid 2-related factor 2 (Nrf2) pathway is one of the most important defensive mechanisms against oxidative stresses and has been confirmed as a target for stroke treatment. Thus, we desired to find new ...

    journal_title:Antioxidants & redox signaling

    pub_type: 杂志文章

    doi:10.1089/ars.2016.6885

    authors: Wu G,Zhu L,Yuan X,Chen H,Xiong R,Zhang S,Cheng H,Shen Y,An H,Li T,Li H,Zhang W

    更新日期:2017-10-10 00:00:00

  • Antiatherogenic effect of bisvanillyl-hydralazone, a new hydralazine derivative with antioxidant, carbonyl scavenger, and antiapoptotic properties.

    abstract::Reactive oxygen species (ROS) generated within the vascular wall trigger low-density lipoprotein (LDL) oxidation, lipid peroxidation, and carbonyl stress that are involved in atherogenesis. We recently reported that the antihypertensive drug, hydralazine, exhibits carbonyl scavenger and antiatherogenic properties, but...

    journal_title:Antioxidants & redox signaling

    pub_type: 杂志文章

    doi:10.1089/ars.2010.3321

    authors: Bouguerne B,Belkheiri N,Bedos-Belval F,Vindis C,Uchida K,Duran H,Grazide MH,Baltas M,Salvayre R,Nègre-Salvayre A

    更新日期:2011-06-01 00:00:00