Reactive oxygen species in oncogenic transformation

2003 ◽  
Vol 31 (6) ◽  
pp. 1441-1444 ◽  
Author(s):  
L. Behrend ◽  
G. Henderson ◽  
R.M. Zwacka

Ever since ROS (reactive oxygen species) were shown to meet the criteria of true signalling molecules, such as regulated production and a specific biological function, many efforts have been made to understand the precise role of ROS. The function of ROS in pathological mechanisms is taking a more and more central role in various fields of biomedical research, including neurobiology, cardiology and cancer. An elevated oxidative status has been found in many types of cancer cells, and the introduction of chemical and enzymological antioxidants can inhibit tumour cell proliferation, pointing to a critical role of ROS in mediating loss of growth control. The present review describes ROS-regulated mechanisms that are associated with cancer and tumour invasiveness. The cellular processes that are linked to these ROS functions are mitogenic signalling and cell motility, while ROS have also been implicated in apoptosis and cellular senescence, two mechanisms regarded as being anti-tumorigenic. This ‘two-faced’ character of free radicals will be discussed and placed in the context of the physiological conditions of the tumour cell, the different molecular backgrounds, and the specific ROS. More detailed understanding of the signalling pathways regulated by ROS in tumour cells will open up new prospects for chemo- or gene-therapeutic interventions.

Blood ◽  
2021 ◽  
Author(s):  
Huan Cai ◽  
Makoto Kondo ◽  
Lakshmi Sandhow ◽  
Pingnan Xiao ◽  
Anne-Sofie Johansson ◽  
...  

Impairement of normal hmatopoiesis and leukemia progression are two well-linked processes during leukemia development and controlled by the bone marrow (BM) niche. Extracellular matrix proteins including laminin are important BM niche components. However, their role in hematopoiesis regeneration and leukemia is unknown. Laminin α4 (Lama4), a major receptor-binding chain of several laminins, is altered in BM niches in mice with acute myeloid leukemia (AML). So far, the impact of Lama4 on leukemia progression remains unknown. We here report that Lama4 deletion in mice resulted in impaired hematopoiesis regeneration following irradiation-induced stress, which is accompanied with altered BM niche composition and inflammation. Importantly, in a transplantation-induced MLL-AF9 AML mouse model, we demonstrate accelerated AML progression and relapse in Lama4-/-mice. Upon AML exposure, Lama4-/- mesenchymal stem cells (MSCs) exhibited dramatic molecular alterations including upregulation of inflammatory cytokines that favor AML growth. Lama4-/- MSCs displayed increased anti-oxidant activities and promoted AML stem cell proliferation and chemoresistance to cytarabine, which was accompanied by increased mitochondrial transfer from the MSCs to AML cells and reduced reactive oxygen species in AML cells in vitro. Similarly, we detected lower levels of reactive oxygen species in AML cells from Lama4-/- mice post-cytarabine treatment. Notably, LAMA4 inhibition or knockdown in human MSCs promoted human AML cell proliferation and chemoprotection. Together, our study for the first time demonstrates a critical role of Lama4 in impeding AML progression and chemoresistance. Targeting Lama4 signaling pathways may offer potential new therapeutic options for AML.


2020 ◽  
Vol 11 (3) ◽  
pp. 4560-4568
Author(s):  
Sunita S Patil ◽  
Vaishali S Patil ◽  
Arvind Gulbake

Throughout several regular cell cycles, reactive oxygen species (ROS) play a critical role. When ROS values are high, and when the defence mechanism (antioxidants) cannot neutralise, they harm and modify the part of biological molecules. They also act as signalling molecules which generate a spectrum of disease.In this study, we reviewed existing oxidants, oxidative stress, and their relationship with infection by human immunodeficiency virus in patients, and the effects of oxidative stress in patients with HIV.Our prospect is to do a clinical study on HIV patients and estimate oxidative parameters like nitric oxide, total antioxidant level and correlate them with CD4 count and viral load which may be helpful during monitoring and giving efficient ART to the HIV patients. And also the importance of ROS in infection has been established through clinical and in vitro studies. Here we review the role of oxidative stress in HIV pathogenesis, the impact of ROS on immune responses in HIV patients, and ROS-mediated regulation of HIV infection. Future studies on the interplay between ROS and HIV infection may offer a new strategy for prevention and treatment.


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