The international team is looking at how selenium could help fight ovarian cancer

Accumulation of SeNPs 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 (between 0.5 and 5 µm) are shown in the figures. SeNP accumulation was observed in vesicles and mitochondria. SKOV-3 shows limited accumulation of SeNPs. All images are representative of at least 3 biological replicates. SKOV-3 and OVCAR-3 cell spheroids were treated for 24 h with selenite or SeNPs and profiled autophagy markers (c). Control and selenite-treated SKOV-3 showed similar levels of ATG5 (0.53 and 0.59, respectively), while SeNP-BSA-treated cells showed a significant increase (0.79, p = 0 .05) of ATG5 levels. SKOV-3 cells treated with SeNP-chitosan showed a non-significant increased level of ATG5 (0.68). Selenite, but not SeNPs, significantly increased LC3B levels in SKOV-3 cells. OVCAR-3 cells showed an increase in ATG5 expression in the different conditions (selenite 0.65, SeNP-BSA 0.56, SeNP-chitosan 0.87) compared to 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 (no treatment) for each treatment. To determine nanoparticle penetration, SKOV-3 cells were treated with FITC-tagged-SeNP-BSA for 24 h (d). Confocal microscope image (Ex 495 nm/Em 521 nm) shows 50 µm z-stacks of a 300 µm diameter spheroid (100 µm bare scale). Local fluorescence was observed inside the spheroid indicating 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 that selenium actually has anti-cancer properties when used in high doses.

To overcome problems with its inherent toxicity, an international research team, led by Professor Steve Conlan at Swansea University and Professor Laurent Charlet at Université Grenoble Alpes, looked at 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 selenium nanoparticles were very effective in killing ovarian cancer cell models that were grown in 3D to mimic the tumor’s natural environment.

They then discovered a new biological mechanism that supports how selenium is likely to cause this anti-cancer effect. They found that selenium causes changes in the activity of enzymes called histone methyltransferases. These enzymes regulate epigenetic processes – how environmental conditions can change the way genes work. Unlike genetic mutations, epigenetic changes do not change the DNA sequence and are reversible, but they change the way 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 Strategic Partnership, and Dr. Noor Al Kafri, a CARA collaborator in Prof. Conlan’s lab, 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 School of Medicine, described the project as a huge scientific research effort. “This is one of those very rare moments when you realize that the team has made a new biological discovery. Noor and Benoit are incredibly talented scientists and it is only through their skill and dedication that we have been able to make this breakthrough. The Swansea- Grenoble clearly shows how international and interdisciplinary collaborations lead the way to scientific discovery.”

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

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

Provided by Swansea University

Reference: International team looks at how selenium could help fight ovarian cancer (2023, March 10) Retrieved March 11, 2023, from ovarian-cancer.html

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