Control of cell proliferation by reactive oxygen species

Abstract Diffuse midline gliomas (DMGs) are highly invasive, unresectable tumors in children. To date, there is no effective treatment for DMGs. Fractionated radiotherapy (RT), currently the standard of care, has provided limited disease control. Current obstacles to treatment include the blood brain barrier (BBB) that limits systemic drug delivery, tumor therapy resistance, and brainstem infiltration. Given the unmet need for more effective DMG treatments, photodynamic therapy (PDT), with the precursor photosensitizing agent 5-aminolevulinic acid (5-ALA), is an oncologic treatment that holds promise. 5-ALA PDT of tumors occurs by targeting tumor cells that accumulate the 5-ALA metabolite, protoporphyrin IX (PPIX), with 635 nm light to create deadly reactive oxygen species (ROS). We explore the synergism of 5-ALA PDT with the MEK inhibitor, trametinib, since the RAS/MEK signaling pathway regulates tumor cell proliferation and survival and has been shown to therapeutically enhance PDT in select tumor models. We demonstrated that sub-micromolar levels of 5-ALA PDT and nanomolar levels of trametinib successfully decrease cell proliferation and induce apoptosis in multiple DMG cell lines. Cell viability assays revealed that drug response differs based on the histone mutation (H3.1 or H3.3) of the line. Mechanisms of decreased cell survival involves the generation of reactive oxygen species that induces programmed cell death. Through the use of a DMG genetically engineered mouse model, we also found 5-ALA PDT to induce apoptosis in vivo. The synergistic effects of MEK inhibition and 5-ALA PDT in vitro and apoptotic effects of 5-ALA PDT in vivo, highlights the potential therapeutic efficacy of this treatment modality.

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A new mechanism for flow-mediated vasoprotection? Focus on “Lung endothelial cell proliferation with decreased shear stress is mediated by reactive oxygen species”

AJP Cell Physiology ◽

10.1152/ajpcell.00414.2005 ◽

2006 ◽

Vol 290 (1) ◽

pp. C35-C36 ◽

Cited By ~ 7

Author(s):

Hua Cai

Keyword(s):

Reactive Oxygen Species ◽

Cell Proliferation ◽

Shear Stress ◽

Endothelial Cell ◽

Reactive Oxygen ◽

Endothelial Cell Proliferation ◽

Oxygen Species

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The Effect of Physical Training on Peripheral Blood Mononuclear Cell Ex Vivo Proliferation, Differentiation, Activity, and Reactive Oxygen Species Production in Racehorses

Antioxidants ◽

10.3390/antiox9111155 ◽

2020 ◽

Vol 9 (11) ◽

pp. 1155

Author(s):

Olga Witkowska-Piłaszewicz ◽

Rafał Pingwara ◽

Anna Winnicka

Keyword(s):

Reactive Oxygen Species ◽

Cell Proliferation ◽

Immune Cell ◽

Ex Vivo ◽

Exercise Physiology ◽

Reactive Oxygen ◽

Oxygen Species ◽

Peripheral Blood Mononuclear ◽

Before And After ◽

Anti Inflammatory

Physical activity has an influence on a variety of processes in an athlete’s organism including the immune system. Unfortunately, there is a lack of studies regarding racehorse immune cells, especially when the horse model is compared to human exercise physiology. The aim of the study was to determine changes in immune cell proliferation, lymphocyte populations, and monocyte functionality in trained and untrained racehorses after exercise. In this study, field data were collected. The cells from 28 racehorses (14 untrained and 14 well-trained) were collected before and after exercise (800 m at a speed of about 800 m/min) and cultured for 4 days. The expression of CD4, CD8, FoxP3, CD14, MHCII, and CD5 in PBMC, and reactive oxygen species (ROS) production, as well as cell proliferation, were evaluated by flow cytometry. In addition, IL-1β, IL-4, IL-6, IL-10, IL-17, INF-γ, and TNF-α concentrations were evaluated by ELISA. The creation of an anti-inflammatory environment in well-trained horses was confirmed. In contrast, a pro-inflammatory reaction occurred in untrained horses after training. In conclusion, an anti-inflammatory state occurs in well-trained racehorses, which is an adaptational reaction to an increased workload during training.

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