Exposure to Selenomethionine and Selenocystine Induces Redox-Mediated ER Stress in Normal Breast Epithelial MCF-10A Cells.

Publisher: Humana Press Country of Publication: United States NLM ID: 7911509 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1559-0720 (Electronic) Linking ISSN: 01634984 NLM ISO Abbreviation: Biol Trace Elem Res Subsets: MEDLINE

Original Publication: [London, Clifton, N. J.] Humana Press.

Selenomethionine*/pharmacology ; Endoplasmic Reticulum Stress*/drug effects ; Cystine*/analogs & derivatives ; Cystine*/pharmacology ; Organoselenium Compounds*/pharmacology ; Epithelial Cells*/metabolism ; Epithelial Cells*/drug effects ; Breast*/cytology ; Breast*/metabolism ; Breast*/drug effects; Humans ; Endoplasmic Reticulum Chaperone BiP ; Oxidation-Reduction/drug effects ; Female ; Apoptosis/drug effects ; Selenocysteine/pharmacology ; Cell Proliferation/drug effects ; MCF-7 Cells ; HeLa Cells

Competing Interests: Declarations. Ethics Approval and Consent to Participate: Not applicable. Competing Interests: The authors declare no competing interests.
Selenium is an essential trace element co-translationally incorporated into selenoproteins with important biological functions. Health benefits have long been associated with selenium supplementation. However, cytotoxicity is observed upon excessive selenium intake. The aim of this study is to investigate the metabolic pathways underlying the response to the selenium-containing amino acids selenomethionine and selenocysteine in a normal human breast epithelial cell model. We show that both selenomethionine and selenocystine inhibit the proliferation of non-cancerous MCF-10A cells in the same concentration range as cancerous MCF-7 and Hela cells, which results in apoptotic cell death. Selenocystine exposure in MCF-10A cells caused a severe depletion of free low molecular weight thiols, which might explain the observed upregulation of the expression of the oxidative stress pathway transcription factor NRF2. Both selenomethionine and selenocystine induced the expression of target genes of the unfolded protein response (GRP78, ATF4, CHOP). Using a redox-sensitive fluorescent probe targeted to the endoplasmic reticulum (ER), we show that both selenoamino acids shifted the ER redox balance towards an even more oxidizing environment. These results suggest that alteration of the redox state of the ER may disrupt protein folding and cause ER stress-induced apoptosis in MCF-10A cells exposed to selenoamino acids.
(© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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Keywords: ER stress; MCF-10A; Oxidative stress; Redox; Selenocystine; Selenomethionine

964MRK2PEL (Selenomethionine)
0 (Endoplasmic Reticulum Chaperone BiP)
1464-43-3 (selenocystine)
48TCX9A1VT (Cystine)
0 (HSPA5 protein, human)
0 (Organoselenium Compounds)
0CH9049VIS (Selenocysteine)

Date Created: 20240522 Date Completed: 20250422 Latest Revision: 20250422

20250423

10.1007/s12011-024-04244-y

38777874