Related Experiment Video
Updated: Apr 28, 2026
Development of an Insert Co-culture System of Two Cellular Types in the Absence of Cell-Cell Contact
Published on: July 17, 2016
Selenium suppresses leukemia through the action of endogenous eicosanoids
Ujjawal H Gandhi1, Naveen Kaushal1, Shailaja Hegde1
1Authors' Affiliations: Department of Veterinary and Biomedical Sciences, Center for Molecular Immunology and Infectious Disease and Center for Molecular Toxicology and Carcinogenesis, The Pennsylvania State University, University Park, Pennsylvania; and.
Selenium targets leukemia cancer stem cells (CSCs) by inducing apoptosis, sparing healthy cells. This dietary micronutrient modulates arachidonic acid metabolism, offering a novel therapeutic strategy for leukemia.
Area of Science:
- Oncology
- Biochemistry
- Hematology
Background:
- Cancer stem cells (CSCs) are crucial for cancer eradication, and their unique metabolic vulnerabilities present therapeutic targets.
- Leukemia CSCs, particularly those derived from chronic or acute myelogenous leukemias, exhibit distinct metabolic characteristics.
- Targeting CSC metabolism is a promising strategy for achieving complete cancer remission.
Purpose of the Study:
- To investigate the potential of the dietary micronutrient selenium in selectively targeting and eradicating leukemia cancer stem cells (CSCs).
- To elucidate the molecular mechanisms by which selenium induces apoptosis in leukemia CSCs.
- To assess the safety and efficacy of selenium treatment in preclinical leukemia models.
Main Methods:
- Treatment of primary human and murine leukemia CSCs with supraphysiologic, nontoxic doses of selenium.
- Analysis of apoptosis pathways, including ATM-p53 activation and reactive oxygen species (ROS) levels.
- Serial transplantation studies in mice to evaluate CSC survival and the role of selenium status.
- Investigation of selenium's reliance on cyclooxygenase-derived prostaglandins (Δ(12)-PGJ2 and 15d-PGJ2) and the impact of NSAIDs and NADPH oxidase inhibitors.
Main Results:
- Selenium administration at supraphysiologic doses triggered apoptosis specifically in leukemia CSCs, while sparing normal hematopoietic stem cells.
- Selenium-induced apoptosis in CSCs was mediated by the ATM-p53 pathway and associated with increased intracellular ROS.
- The efficacy of selenium was dependent on endogenous prostaglandin production (Δ(12)-PGJ2 and 15d-PGJ2) and arachidonic acid metabolism.
- Inhibition of prostaglandin synthesis or NADPH oxidase activity abrogated selenium's apoptotic effect on leukemia CSCs.
Conclusions:
- Dietary selenium, at specific doses, can selectively induce apoptosis in leukemia cancer stem cells.
- Selenium's mechanism involves the ATM-p53 pathway, ROS generation, and modulation of arachidonic acid metabolism via prostaglandins.
- This study highlights selenium as a potential therapeutic agent for leukemia, targeting CSCs without harming normal stem cells.
