Related Experiment Video
Updated: May 3, 2026
Generation and Expansion of Primary, Malignant Pleural Mesothelioma Tumor Lines
Published on: April 21, 2022
Increasing dietary selenium elevates reducing capacity and ERK activation associated with accelerated progression of
Aaron H Rose1, Pietro Bertino1, FuKun W Hoffmann1
1Department of Cell and Molecular Biology, John A. Burns School of Medicine, University of Hawai'i, Honolulu, Hawaii.
Abstract:
To study the effect of the micronutrient selenium on malignant mesothelioma (MM) progression, we cultured four different MM cell lines in media containing increasing amounts of sodium selenite (30, 50, and 80 nmol/L). Increasing selenium levels increased density-dependent proliferation and mobility for CRH5 and EKKH5 but not AB12 and AK7. Comparing these cell lines revealed that extracellular regulated kinase (ERK) phosphorylation was sensitive to a selenium increase in CRH5 and EKKH5 but not AB12 and AK7 cells. Stable expression of a dominant-negative mutant ERK eliminated the effects of increasing selenium. Because ERK is redox sensitive, we compared the MM cell lines in terms of glutathione levels and the capacity to reduce exogenous hydrogen peroxide. Increasing selenium levels led to higher glutathione and reducing capacity in CRH5 and EKKH5 but not AB12 and AK7. The reducing agent N-acetylcysteine eliminated the effects of selenium on ERK activation, proliferation, and mobility. Mice fed diets containing increasing levels of selenium (0.08, 0.25, and 1.0 ppm) showed increased tumor progression for CRH5 but not AB12, MM cells, and in vivo N-acetylcysteine treatment eliminated these effects. These data suggest that the effects of dietary selenium on MM tumor progression depend on the arising cancer cells' redox metabolism, and the tumors able to convert increased selenium into a stronger reducing capacity actually benefit from increased selenium intake.
Insights
Dietary selenium intake impacts malignant mesothelioma (MM) progression. MM cells with higher redox capacity benefit from increased selenium, enhancing tumor growth, while others show no effect. N-acetylcysteine counteracted these selenium-driven changes.
Area of Science:
- Oncology
- Cell Biology
- Nutritional Science
Background:
- Malignant mesothelioma (MM) is an aggressive cancer.
- The role of micronutrients like selenium in MM progression is not fully understood.
- Cellular redox metabolism may influence MM cell responses to selenium.
Purpose of the Study:
- To investigate the effect of selenium on MM cell proliferation, mobility, and tumor progression.
- To explore the underlying mechanisms, focusing on cellular redox status and extracellular regulated kinase (ERK) signaling.
- To determine if N-acetylcysteine can modulate selenium's effects on MM.
Main Methods:
- Cultured four MM cell lines with varying sodium selenite concentrations.
- Assessed proliferation, mobility, and ERK phosphorylation.
- Measured glutathione levels and hydrogen peroxide reducing capacity.
- Utilized dominant-negative ERK mutant and N-acetylcysteine treatment.
- Administered varying selenium levels in mouse diets and treated with N-acetylcysteine.
Main Results:
- Increased selenium enhanced proliferation and mobility in CRH5 and EKKH5 MM cells, but not AB12 and AK7.
- Selenium increased glutathione levels and reducing capacity in CRH5 and EKKH5 cells.
- ERK phosphorylation was sensitive to selenium in CRH5 and EKKH5 cells.
- N-acetylcysteine reversed selenium-induced effects on ERK, proliferation, and mobility.
- In vivo, increased dietary selenium promoted tumor progression in CRH5 MM-bearing mice, an effect abolished by N-acetylcysteine.
Conclusions:
- The impact of selenium on MM progression is contingent upon the cancer cells' intrinsic redox metabolism.
- MM cells with a robust capacity to enhance their reducing potential benefit from increased selenium, leading to accelerated tumor growth.
- Targeting cellular redox pathways, such as with N-acetylcysteine, may offer therapeutic strategies to mitigate adverse selenium effects in MM.
