Prostate cancer is a leading cause of cancer death in men. Inflammation and overexpression of inducible nitric oxide synthase (NOS2) have been implicated in prostate carcinogenesis. We aimed to explore the hypothesis that nitric oxide NO exerts pro-tumorigenic effects on prostate cells at physiologically relevant levels contributing to carcinogenesis. We investigated the impact of acute exposure of normal immortalised prostate cells (RWPE-1) to NO on cell proliferation and activation of DNA damage repair pathways. Furthermore we investigated the long term effects of chronic NO exposure on RWPE-1 cell migration and invasion potential and hallmarks of transformation. Our results demonstrate that NO induces DNA damage as indicated by γH2AX foci and p53 activation resulting in a G1/S phase block and activation of 53BP1 DNA damage repair protein. Long term adaption to NO results in increased migration and invasion potential, acquisition of anchorage independent growth and increased resistance to chemotherapy. This was recapitulated in PC3 and DU145 prostate cancer cells which upon chronic exposure to NO displayed increased cell migration, colony formation and increased resistance to chemotherapeutics. These findings indicate that NO may play a key role in the development of prostate cancer and the acquisition of an aggressive metastatic phenotype.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.niox.2022.07.005 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Endothelin receptor antagonists (ERAs) can potentially be used as therapeutic drugs to reduce hypertension caused by small molecule tyrosine kinase inhibitors (TKIs).
Front Pharmacol
January 2025
Department of Cardiovascular Center, First Affiliated Hospital of Huzhou University, Huzhou, China.
The emergence of targeted anti-tumor drugs has significantly prolonged the lifespan and improved the prognosis of cancer patients. Among these drugs, vascular endothelial growth factor (VEGF) inhibitors, particularly novel small molecule tyrosine kinase inhibitors (TKIs), are extensively employed as VEGF inhibitors; however, they are also associated with a higher incidence of complications, with hypertension being the most prevalent cardiovascular toxic side effect. Currently, it is widely accepted that TKIs-induced hypertension involves multiple mechanisms including dysregulation of the endothelin (ET) axis, reduced bioavailability of nitric oxide (NO), imbalance in NO-ROS equilibrium system, vascular rarefaction, and activation of epithelial sodium calcium channels; nevertheless, excessive activation of ET system appears to be predominantly responsible for this condition.
View Article and Find Full Text PDFProtective effects of berbamine against arginase-1 deficiency-induced injury in human brain microvascular endothelial cells.
Front Pharmacol
January 2025
Department of Geriatric Medicine, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong, China.
Endothelial cell dysfunction plays a crucial role in the early development of cerebral small vessel disease (CSVD). Arginase-1 (ARG1) is expressed in endothelial cells, and its deficiency may exacerbate cerebrovascular damage by increasing reactive oxygen species (ROS) production, thereby inducing endothelial cell apoptosis. Berbamine (BBM) has shown potential in neuroprotection and cardiovascular disease prevention.
View Article and Find Full Text PDFNitric oxide in exercise physiology: past and present perspectives.
Front Physiol
January 2025
School of Kinesiology, Auburn University, Auburn, AL, United States.
Nitric oxide (NO) is a ubiquitous signaling molecule known to modulate various physiological processes, with specific implications in skeletal muscle and broader applications in exercise performance. This review focuses on the modulation of skeletal muscle function, mitochondrial adaptation and function, redox state by NO, and the effect of nitrate supplementation on exercise performance. In skeletal muscle function, NO is believed to increase the maximal shortening velocity and peak power output of muscle fibers.
View Article and Find Full Text PDFChloroform Extract from Fermented Regulates LPS-Induced Inflammation Response in RAW 264.7 Cells by Inhibiting iNOS and COX-2.
J Microbiol Biotechnol
December 2024
Department of Medicinal Biotechnology, College of Health Sciences, Dong-A University, Busan 49315, Republic of Korea.
Inflammatory is a crucial part of the immune system of body protect it from harmful invaders, such as bacteria, viruses, and other foreign substances. In this study, the effects of chloroform extract of fermented (CEFV) on lipopolysaccharide (LPS)-induced inflammatory response in RAW264.7 macrophages were investigated.
View Article and Find Full Text PDFSynergistic anti-oxidative/anti-inflammatory treatment for acute lung injury with selenium based chlorogenic acid nanoparticles through modulating Mapk8ip1/MAPK and Itga2b/PI3k-AKT axis.
J Nanobiotechnology
January 2025
School of Life Sciences, Faculty of Medicine, Tianjin University, Tianjin, 300072, China.
Oxidative stress and inflammatory dysregulation play crucial roles in pathogenesis of acute lung injury (ALI), and their cyclic synergy drives excessive inflammatory responses and further exacerbates ALI. Therefore, new effective strategies to treat ALI are urgently needed. Herein, a novel synergistic selenium based chlorogenic acid nanoparticle was developed to disrupt the cyclic synergistic effect between oxidative stress and inflammatory response in ALI.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!