Oncogenic pathways and the electron transport chain: a dangeROS liaison

Raimondi, Vittoria; Ciccarese, Francesco; Ciminale, Vincenzo

doi:10.1038/s41416-019-0651-y

Cited by 135 publications

(115 citation statements)

References 210 publications

(135 reference statements)

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“…In many types of tumor cells these higher levels support their growth, proliferation, metastasis and survival in various microenvironments or conditions. Low to medium levels of ROS can lead to genetic instability and tumor suppression (see recent reviews of [ 32 , 33 ]).…”

Section: Glutathione Redox and Ros In Healthy And Tumor Cellsmentioning

confidence: 99%

Role of Glutathione in Cancer: From Mechanisms to Therapies

et al. 2020

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Glutathione (GSH) is the most abundant non-protein thiol present at millimolar concentrations in mammalian tissues. As an important intracellular antioxidant, it acts as a regulator of cellular redox state protecting cells from damage caused by lipid peroxides, reactive oxygen and nitrogen species, and xenobiotics. Recent studies have highlighted the importance of GSH in key signal transduction reactions as a controller of cell differentiation, proliferation, apoptosis, ferroptosis and immune function. Molecular changes in the GSH antioxidant system and disturbances in GSH homeostasis have been implicated in tumor initiation, progression, and treatment response. Hence, GSH has both protective and pathogenic roles. Although in healthy cells it is crucial for the removal and detoxification of carcinogens, elevated GSH levels in tumor cells are associated with tumor progression and increased resistance to chemotherapeutic drugs. Recently, several novel therapies have been developed to target the GSH antioxidant system in tumors as a means for increased response and decreased drug resistance. In this comprehensive review we explore mechanisms of GSH functionalities and different therapeutic approaches that either target GSH directly, indirectly or use GSH-based prodrugs. Consideration is also given to the computational methods used to describe GSH related processes for in silico testing of treatment effects.

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Section: Glutathione Redox and Ros In Healthy And Tumor Cellsmentioning

confidence: 99%

Role of Glutathione in Cancer: From Mechanisms to Therapies

et al. 2020

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“…ROS bear the harmful potential to oxidize lipids, nucleic acids, and proteins making mitochondria the etiological origin of metabolic and degenerative diseases as well as aging [ 101 , 102 , 103 ]. ROS are unavoidably generated by enzymes of the mitochondrial electron transport chain (ETC) during side reactions of electrons with molecular oxygen [ 104 ]. Other mitochondrial oxidoreductases reported to generate ROS are glycerol-3-phosphate dehydrogenase, dihydroorotate dehydrogenase, electron-transfer flavoprotein-ubiquinone oxidoreductase (ETF:QO), proline oxidase, and the dihydrolipoamide dehydrogenase subcomplex of α-ketoacid dehydrogenases including pyruvate, α-ketoglutarate, α-ketoadipate, and branched-chain α-ketoacid dehydrogenase [ 105 ].…”

Section: Reactive Oxygen Species and Cancer—a Dangerous Liaisonmentioning

confidence: 99%

The Impact of Mitochondrial Fission-Stimulated ROS Production on Pro-Apoptotic Chemotherapy

Ježek

Cooper

Strich

2021

Biology

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Cancer is one of the world’s deadliest afflictions. Despite recent advances in diagnostic and surgical technologies, as well as improved treatments of some individual tumor types, there is currently no universal cure to prevent or impede the uncontrolled proliferation of malignant cells. Targeting tumors by inducing apoptosis is one of the pillars of cancer treatment. Changes in mitochondrial morphology precede intrinsic apoptosis, but mitochondrial dynamics has only recently been recognized as a viable pharmacological target. In many cancers, oncogenic transformation is accompanied by accumulation of elevated cellular levels of ROS leading to redox imbalance. Hence, a common chemotherapeutic strategy against such tumor types involves deploying pro-oxidant agents to increase ROS levels above an apoptotic death-inducing threshold. The aim of this chapter is to investigate the benefit of stimulating mitochondrial fission-dependent production of ROS for enhanced killing of solid tumors. The main question to be addressed is whether a sudden and abrupt change in mitochondrial shape toward the fragmented phenotype can be pharmacologically harnessed to trigger a burst of mitochondrial ROS sufficient to initiate apoptosis specifically in cancer cells but not in non-transformed healthy tissues.

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“…While low/medium levels of ROS promote mitogenic signaling through reversible oxidation of cysteines to sulfenic acid [5] and disulfide bonds [6], high levels of ROS exert cytotoxic effects by inducing base oxidation in nucleic acids and lipid peroxidation, resulting in cell death, which may trigger inflammation and fibrosis. In cancer cells, activation of oncogenic pathways boosts ROS production by the mitochondrial electron transport chain (ETC) [7] and nonmitochondrial oxidases. The increased activity of ROS-scavenging pathways partly curbs such an increase in ROS production.…”

Section: Importance Of Reactive Oxygen Species In Cancer Therapymentioning

confidence: 99%

Nanoparticles as Tools to Target Redox Homeostasis in Cancer Cells

et al. 2020

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Reactive oxygen species (ROS) constitute a homeostatic rheostat that modulates signal transduction pathways controlling cell turnover. Most oncogenic pathways activated in cancer cells drive a sustained increase in ROS production, and cancer cells are strongly addicted to the increased activity of scavenging pathways to maintain ROS below levels that produce macromolecular damage and engage cell death pathways. Consistent with this notion, tumor cells are more vulnerable than their normal counterparts to pharmacological treatments that increase ROS production and inhibit ROS scavenging. In the present review, we discuss the recent advances in the development of integrated anticancer therapies based on nanoparticles engineered to kill cancer cells by raising their ROS setpoint. We also examine nanoparticles engineered to exploit the metabolic and redox alterations of cancer cells to promote site-specific drug delivery to cancer cells, thus maximizing anticancer efficacy while minimizing undesired side effects on normal tissues.

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Oncogenic pathways and the electron transport chain: a dangeROS liaison

Cited by 135 publications

References 210 publications

Role of Glutathione in Cancer: From Mechanisms to Therapies

Role of Glutathione in Cancer: From Mechanisms to Therapies

The Impact of Mitochondrial Fission-Stimulated ROS Production on Pro-Apoptotic Chemotherapy

Nanoparticles as Tools to Target Redox Homeostasis in Cancer Cells

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