Article

Increasing Dietary Selenium Elevates Reducing Capacity and ERK Activation Associated with Accelerated Progression of Select Mesothelioma Tumors

Department of Cellular and Molecular Biology, John A. Burns School of Medicine, University of Hawaii, Honolulu, Hawaii
American Journal Of Pathology (Impact Factor: 4.59). 01/2014; 184(4). DOI: 10.1016/j.ajpath.2013.12.008
Source: PubMed

ABSTRACT

Dietary selenium is an essential micronutrient. To study the effect of increasing dietary 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 the amounts of selenium increased density-dependent proliferation and mobility for CRH5 and EKKH5, but not AB12 and AK7. Comparison of these cell lines showed 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. 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.

Download full-text

Full-text

Available from: Pietro Bertino, Jul 15, 2014
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Individuals exposed to fibrogenic mineral dust may exhibit an impaired antioxidant system and produce high levels of reactive oxygen and nitrogen species through immune cells, contributing to the perturbation of immune cell function, inflammation, fibrosis and lung cancer. The lung diseases which are caused by inhalation of fibrogenic mineral dust, known as pneumoconioses, develop progressively and irreversibly over decades. At the moment there is no known cure. The trace element selenium has potent antioxidant and anti-inflammatory properties mediated mainly through selenoproteins. Research has demonstrated that selenium has the ability to protect against cardiovascular diseases; to kill cancer cells in vitro and reduce cancer incidence; and to immunomodulate various cellular signaling pathways. For these reasons, selenium has been proposed as a promising therapeutic agent in oxidative stress associated pathology that in theory would be beneficial for the prevention or treatment of pneumoconioses such as silicosis, asbestosis, and coal worker's pneumoconiosis. However, studies regarding selenium and occupational lung diseases are rare. The purpose of this study is to conduct a mini-review regarding the relationship between selenium and exposure to fibrogenic mineral dust with emphasis on epidemiological studies. We carried out a systematic literature search of English published studies on selenium and exposure to fibrogenic mineral dust. We found four epidemiological studies. Reviewed studies show that selenium is lower in individuals exposed to fibrogenic mineral dust. However, three out of the four reviewed studies could not confirm cause-and-effect relationships between low selenium status and exposure to fibrogenic mineral dust. This mini-review underscores the need for large follow-up and mechanistic studies for selenium to further elucidate its therapeutic effects. Copyright © 2015 Elsevier Ltd. All rights reserved.
    Full-text · Article · Jan 2015 · Environment International
  • [Show abstract] [Hide abstract]
    ABSTRACT: The role of reactive oxygen species (ROS) in cancer cells has been intensively studied for the past two decades. Cancer cells mostly have higher basal ROS levels than their normal counterparts. The induction of ROS has been shown to be associated with cancer development, metastasis, progression, and survival. Various therapeutic approaches targeting intracellular ROS levels have yielded mixed results. As widely accepted dietary supplements, antioxidants demonstrate both ROS scavenging ability and anti-cancer characteristics. However, antioxidants may not always be safe to use since excessive intake of antioxidants could lead to serious health concerns. In this review, we have evaluated the production and scavenging systems of ROS in cells, as well as the beneficial and harmful roles of ROS in cancer cells. We also examine the effect of antioxidants in cancer treatment, the effect of combined treatment of antioxidants with traditional cancer therapies, and the side effects of excessive antioxidant intake. Copyright © 2015. Published by Elsevier Ireland Ltd.
    No preview · Article · Jul 2015 · Cancer letters