ROS homeostasis and metabolism: a dangerous liason in cancer cells.
Reads0
Chats0
TLDR
How the mitochondria has a key role in regulating the interplay between redox homeostasis and metabolism within tumor cells is described, and the potential therapeutic use of agents that directly or indirectly block metabolism is discussed.Abstract:
Tumor cells harbor genetic alterations that promote a continuous and elevated production of reactive oxygen species. Whereas such oxidative stress conditions would be harmful to normal cells, they facilitate tumor growth in multiple ways by causing DNA damage and genomic instability, and ultimately, by reprogramming cancer cell metabolism. This review outlines the metabolic-dependent mechanisms that tumors engage in when faced with oxidative stress conditions that are critical for cancer progression by producing redox cofactors. In particular, we describe how the mitochondria has a key role in regulating the interplay between redox homeostasis and metabolism within tumor cells. Last, we will discuss the potential therapeutic use of agents that directly or indirectly block metabolism.read more
Citations
More filters
Journal ArticleDOI
Reactive oxygen species (ROS) as pleiotropic physiological signalling agents.
Helmut Sies,Dean P. Jones +1 more
TL;DR: This work focuses on ROS at physiological levels and their central role in redox signalling via different post-translational modifications, denoted as ‘oxidative eustress’.
Journal ArticleDOI
ROS signalling in the biology of cancer.
TL;DR: The generation and sources of ROS within tumour cells, the regulation of ROS by antioxidant defence systems, as well as the effect of elevated ROS production on their signalling targets in cancer are discussed.
Journal ArticleDOI
ROS in cancer therapy: the bright side of the moon
Bruno Perillo,Marzia Di Donato,Antonio Pezone,Erika Di Zazzo,Pia Giovannelli,Giovanni Galasso,Gabriella Castoria,Antimo Migliaccio +7 more
TL;DR: The review will emphasize the molecular mechanisms useful for the development of therapeutic strategies that are based on modulating ROS levels to treat cancer, and report on the growing data that highlight the role of ROS generated by different metabolic pathways as Trojan horses to eliminate cancer cells.
Journal ArticleDOI
Superoxide dismutases: Dual roles in controlling ROS damage and regulating ROS signaling.
TL;DR: Studies in model organisms and humans are discussed, which reveal the dual roles of SOD enzymes in controlling damage and regulating signaling and the need for fine local control of ROS signaling.
Journal ArticleDOI
ROS Generation and Antioxidant Defense Systems in Normal and Malignant Cells
Anastasiya V. Snezhkina,Anna V. Kudryavtseva,Olga L. Kardymon,Maria V Savvateeva,Nataliya V. Melnikova,George S. Krasnov,Alexey A. Dmitriev +6 more
TL;DR: This review covers the current data on the mechanisms of ROS generation and existing antioxidant systems balancing the redox state in mammalian cells that can also be related to tumors.
References
More filters
Journal ArticleDOI
HIF-dependent antitumorigenic effect of antioxidants in vivo.
Ping Gao,Huafeng Zhang,Ramani Dinavahi,Feng Li,Yan Xiang,Venu Raman,Zaver M. Bhujwalla,Dean W. Felsher,Linzhao Cheng,Jonathan Pevsner,Linda A. Lee,Gregg L. Semenza,Chi V. Dang +12 more
TL;DR: It is reported that antioxidants inhibited three tumorigenic models in vivo and challenge the paradigm that antioxidants diminish tumorigenesis primarily through decreasing DNA damage and mutations and provide significant support for a key antitumorigenic effect of diminishing HIF levels.
Journal ArticleDOI
Inhibition of glutaminase preferentially slows growth of glioma cells with mutant IDH1.
Meghan J. Seltzer,Bryson D. Bennett,Avadhut D. Joshi,Ping Gao,Ajit G. Thomas,Dana Ferraris,Takashi Tsukamoto,Camilo Rojas,Barbara S. Slusher,Joshua D. Rabinowitz,Chi V. Dang,Gregory J. Riggins +11 more
TL;DR: The ability to selectively slow growth in cells with IDH1 mutations by inhibiting glutaminase suggests a unique reprogramming of intermediary metabolism and a potential therapeutic strategy.
Journal ArticleDOI
A Mitochondrial Switch Promotes Tumor Metastasis
Paolo E. Porporato,Valéry Payen,Jhudit Pérez-Escuredo,Christophe De Saedeleer,Pierre Danhier,Tamara Copetti,Suveera Dhup,Morgane Tardy,Thibaut Vazeille,Caroline Bouzin,Olivier Feron,Carine Michiels,Bernard Gallez,Pierre Sonveaux +13 more
TL;DR: Two different events, ETC overload and partial ETC inhibition, promote superoxide-dependent tumor cell migration, invasion, clonogenicity, and metastasis, and specific scavenging of mitochondrial superoxide with mitoTEMPO blocked tumor cell Migration and prevented spontaneous tumor metastasis in murine and human tumor models.
Journal ArticleDOI
Redox regulation of mitochondrial function.
Diane E. Handy,Joseph Loscalzo +1 more
TL;DR: This review examines the regulation of cellular ROS, their modes of production and removal, and the redox-sensitive targets that are modified by their flux and the role of mitochondria in modulating these pathways.
Journal ArticleDOI
Metabolic enzyme expression highlights a key role for MTHFD2 and the mitochondrial folate pathway in cancer
Roland Nilsson,Mohit Jain,Nikhil Madhusudhan,Nina Gustafsson Sheppard,Laura Strittmatter,Caroline Kampf,Jenny Huang,Anna Asplund,Vamsi K. Mootha +8 more
TL;DR: This study compares messenger RNA profiles of 1,454 metabolic enzymes across 1,981 tumours spanning 19 cancer types to identify enzymes that are consistently differentially expressed and highlights the importance of mitochondrial compartmentalization of one-carbon metabolism in cancer and raises important therapeutic hypotheses.