International team examines how selenium could help in fight against ovarian cancer

International team examines how selenium could help in fight against ovarian cancer
SeNP accumulation in SKOV-3 and OVCAR-3 spheroids. SeNPs penetrate and accumulate in SKOV-3 and OVCAR-3 spheroids. SKOV-3 (a) and OVCAR-3 (b) cell spheroids were treated with BSA-SeNPs at IC20 concentrations for 24 h and imaged by TEM. Scale bars are displayed on the images (between 0.5 and 5 μm). SeNP accumulation was observed in vesicles and mitochondria. SKOV-3 show a limited accumulation of SeNPs. All images are representative of a minimum of 3 biological repeats. SKOV-3 and OVCAR-3 cell spheroids were treated for 24 h with selenite or SeNPs and profiling autophagy markers (c). Control and selenite treated SKOV-3 displayed similar levels of ATG5 (respectively 0.53 and 0.59), whereas SeNP-BSA treated cells showed a significant increase (0.79, p = 0.05) of ATG5 levels. SeNP-chitosan treated SKOV-3 cells showed a non-significant elevated level of ATG5 (0.68). Selenite, but not SeNPs, had significantly increased LC3B levels in SKOV-3 cells. OVCAR-3 cells displayed an increase of ATG5 expression in the different conditions (selenite 0.65, SeNP-BSA 0.56, SeNP-chitosan 0.87) compared to the control (0.46) that was only significant for SeNP-chitosan (p < 0.05). Data represent the mean ± SD of three biological replicates *p < 0.05 significant vs respective Control (untreated) for each treatment. To determine nanoparticle penetration, SKOV-3 cells were treated with FITC-tagged-SeNP-BSA for 24 h (d). Confocal microscope (Ex 495 nm/Em 521 nm) imaging shows 50 μm z-stacks of a 300 μm diameter spheroid (scale bare 100 μm). Local fluorescence was observed inside the spheroid demonstrating nanoparticle penetration. Credit: Redox Biology (2023). DOI: 10.1016/j.redox.2023.102641

Selenium is a micronutrient that plays an essential role in human health but is toxic at high levels. However, new biomedical research has shown selenium actually has anti-cancer properties when used at high doses.

To overcome problems with its inherent toxicity, an international research team, led by Professor Steve Conlan in Swansea University and Professor Laurent Charlet at Université Grenoble Alpes, tested whether selenium nanoparticles could be developed as a potential cancer treatment. Their findings have just been published in the journal Redox Biology.

The researchers demonstrated that the selenium nanoparticles were very effective at killing ovarian cancer cell models grown in 3D to replicate the native tumor environment.

They went on to discover a novel biological mechanism underpinning how selenium is likely to cause this anti-cancer effect. They found that selenium causes changes in the activity of enzymes called histone methylatransferases. These enzymes regulate epigenetic processes—how can alter the way genes work. Unlike , epigenetic changes do not change the sequence of DNA and are reversible, but they do change how your body reads a DNA sequence.

This research was carried out by Dr. Benoit Toubans, as part of his joint Ph.D. project supported by the Swansea-Grenoble , and Dr. Noor Al Kafri, a CARA fellow in Professor Conlan's laboratory, together with collaborators at the synchrotron facility in Grenoble and the University of Stuttgart.

Professor Conlan, who heads the Reproductive Biology and Gynecological Oncology group at Swansea University Medical School, described the project as a tremendous scientific research effort. "This is one of those quite rare moments when you realize the team have made a novel biological discovery. Noor and Benoit are incredibly talented scientists, and only through their skill and dedication were we able to make this advance. The Swansea-Grenoble partnership demonstrates clearly how international and interdisciplinary partnerships lead the way in ."

The team hopes this discovery will provide new insights into the action of selenium nanoparticles and says it is now important to consider both the classic antioxidant and novel histone methylation effects of and its development as a cancer therapy

More information: Benoit Toubhans et al, Selenium nanoparticles modulate histone methylation via lysine methyltransferase activity and S-adenosylhomocysteine depletion, Redox Biology (2023). DOI: 10.1016/j.redox.2023.102641

Provided by Swansea University

Citation: International team examines how selenium could help in fight against ovarian cancer (2023, March 10) retrieved 21 March 2023 from
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