Extracellular albumin covalently sequesters selenocompounds and determines cytotoxicity
Zheng, Wenyi (Karolinska Institutet (Estocolm, Suècia). Department of Laboratory Medicine)
Boada, Roberto (Universitat Autònoma de Barcelona. Departament de Química)
He, Riu (Karolinska Institutet (Estocolm, Suècia). Department of Laboratory Medicine)
Xiao, Tingting (Universitat Autònoma de Barcelona. Departament de Química)
Ye, Fei (Kungliga Tekniska högskolan. Division of Functional Nanomaterials)
Simonelli, Laura (ALBA Laboratori de Llum de Sincrotró)
Valiente Malmagro, Manuel (Universitat Autònoma de Barcelona. Departament de Química)
Zhao, Ying (Karolinska Institutet (Estocolm, Suècia). Department of Laboratory Medicine)
Hassan, Moustapha (Karolinska Institutet (Estocolm, Suècia). Department of Laboratory Medicine)

Date:	2019
Abstract:	Selenocompounds (SeCs) are well-known nutrients and promising candidates for cancer therapy; however, treatment efficacy is very heterogeneous and the mechanism of action is not fully understood. Several SeCs have been reported to have albumin-binding ability, which is an important factor in determining the treatment efficacy of drugs. In the present investigation, we hypothesized that extracellular albumin might orchestrate SeCs efficacy. Four SeCs representing distinct categories were selected to investigate their cytotoxicity, cellular uptake, and species transformation. Concomitant treatment of albumin greatly decreased cytotoxicity and cellular uptake of SeCs. Using both X-ray absorption spectroscopy and hyphenated mass spectrometry, we confirmed the formation of macromolecular conjugates between SeCs and albumin. Although the conjugate was still internalized, possibly via albumin scavenger receptors expressed on the cell surface, the uptake was strongly inhibited by excess albumin. In summary, the present investigation established the importance of extracellular albumin binding in determining SeCs cytotoxicity. Due to the fact that albumin content is higher in humans and animals than in cell cultures, and varies among many patient categories, our results are believed to have high translational impact and clinical implications.
Grants:	European Commission 778325 European Commission 665919 Ministerio de Economía y Competitividad CTM2015-65414-C2-1-R
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Selenium ; Albumin ; Cytotoxicity ; Cellular uptake ; X-ray absorption spectroscopy
Published in:	International journal of molecular sciences, Vol. 20, issue 19 (Oct. 2019) , art. 4734, ISSN 1422-0067

DOI: 10.3390/ijms20194734
PMID: 31554226

13 p, 1.8 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Experimental sciences > The ALBA Synchrotron
Articles > Research articles
Articles > Published articles