Plasma membrane permeabilization to explain erythrosine B phototoxicity on in vitro breast cancer cell models

Autor(es)

Bistaffa, Maria J. ^[1] ; Camacho, Sabrina A. ^{[2, 1]} ; Melo, Carlos F. O. R. ^[1] ; Catharino, Rodrigo R. ^[3] ; Toledo, Karina A. ^{[1, 4]} ; Aoki, Pedro H. B. ^[1]

Afiliação do(s) autor(es)

^[1] Sao Paulo State Univ, UNESP, Sch Sci Humanities & Languages, BR-19806900 Assis, SP - Brazil

^[2] Univ Sao Paulo, Sao Carlos Inst Phys, IFSC, BR-13566590 Sao Carlos, SP - Brazil

^[3] Univ Estadual Campinas, Sch Pharmaceut Sci, INNOVARE Biomarkers Lab, BR-13083970 Campinas, SP - Brazil

^[4] Sao Paulo State Univ, UNESP, Inst Biosci Letters & Exact Sci, BR-15054000 Sao Jose Do Rio Preto, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY; v. 223, OCT 2021.
• Citações Web of Science: 0

Resumo

Lipid oxidation is ubiquitous in cell life under oxygen and essential for photodynamic therapy (PDT) of carcinomas. However, the mechanisms underlying lipid oxidation in rather complex systems such as plasma membranes remain elusive. Herein, Langmuir monolayers were assembled with the lipid extract of glandular breast cancer (MCF7) cells and used to probe the molecular interactions allowing adsorption of the photosensitizer (PS) erythrosine B and subsequent photooxidation outcomes. Surface pressure (pi) versus area (cm2/mL) isotherms of MCF7 lipid extract shifted to larger areas upon erythrosine incorporation, driven by secondary interactions that affected the orientation of the carbonyl groups and lipid chain organization. Light-irradiation increased the surface area of the MCF7 lipid extract monolayer containing erythrosine owing to the lipid hydroperoxidation, which may further undergo decomposition, resulting in the chain cleavage of phospholipids and membrane permeabilization. Incorporation of erythrosine by MCF7 cells induced slight toxic effects on in vitro assays, differently of the severe phototoxicity caused by light-irradiation, which significantly decreased cell viability by more than 75% at 2.5 x 10-6 mol/L of erythrosine incubated for 3 and 24 h, reaching nearly 90% at 48 h of incubation. The origin of the phototoxic effects is in the rupture of the plasma membrane shown by the frontal (FSC) and side (SSC) light scattering of flow cytometry. Consistent with hydroperoxide decomposition, membrane permeabilization was also confirmed by cleaved lipids detected in mass spectrometry and subsidizes the necrotic pathway of cell death. (AU)

• Processo FAPESP: 18/14692-5 - Terapia fototérmica mediada por nanopartículas de ouro: de sistemas modelos de biomembranas ao cultivo in vitro de células tumorais
• Beneficiário: Sabrina Aléssio Camacho
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 13/14262-7 - Filmes nanoestruturados de materiais de interesse biológico
• Beneficiário: Osvaldo Novais de Oliveira Junior
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 16/20576-2 - Fotossensibilização de células derivadas do carcinoma de orofaringe (HEp-2) induzida pela ação do xantênico eritrosina
• Beneficiário: Maria Julia Bistaffa
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica
• Processo FAPESP: 18/16713-0 - Terapia fotodinâmica: de efeitos moleculares em sistemas modelos a eficiência fotodinâmica em cultivo celular
• Beneficiário: Pedro Henrique Benites Aoki
• Modalidade de apoio: Auxílio à Pesquisa - Regular