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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Effects of ICI 182,780, an ER alpha and ER beta antagonist, and G-1, a GPER agonist, on autophagy in breast cancer cells

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Muler, Mari Luminosa [1] ; Antunes, Fernanda [1] ; Guarache, Gabriel Cicolin [1] ; Oliveira, Rafaela Brito [2] ; Ureshino, Rodrigo Portes [2] ; Bincoletto, Claudia [1] ; da Silva Pereira, Gustavo Jose [1] ; Smaili, Soraya Soubhi [1]
Total Authors: 8
[1] Univ Fed Sao Paulo, Escola Paulista Med, Dept Farmacol, Sao Paulo, SP - Brazil
[2] Univ Fed Sao Paulo, Dept Ciencias Biol, Diadema, SP - Brazil
Total Affiliations: 2
Document type: Journal article
Source: Einstein (São Paulo); v. 18, 2020.
Web of Science Citations: 0

Objective: To investigate if ICI 182,780 (fulvestrant), a selective estrogen receptor alpha/beta (ER alpha/ER beta) antagonist, and G-1, a selective G-protein-coupled receptor (GPER) agonist, can potentially induce autophagy in breast cancer cell lines MCF-7 and SKBr3, and how G-1 affects cell viability. Methods: Cell viability in MCF-7 and SKBr3 cells was assessed by the MIT assay. To investigate the autophagy flux, MCF-7 cells were transfected with GFP-LC3, a marker of autophagosomes, and analyzed by real-time fluorescence microscopy. MCF-7 and SKBr3 cells were incubated with acridine orange for staining of acidic vesicular organelles and analyzed by flow cytometry as an indicator of autophagy. Results: Regarding cell viability in MCF-7 cells, ICI 182,780 and rapamycin, after 48 hours, led to decreased cell proliferation whereas G-1 did not change viability over the same period. The data showed that neither ICI 182,780 nor G-1 led to increased GFP-LC3 puncta in MCF-7 cells over the 4-hour observation period. The cytometry assay showed that ICI 182,780 led to a higher number of acidic vesicular organelles in MCF-7 cells. G-1, in turn, did not have this effect in any of the cell lines. In contrast, ICI 182,780 and G-1 dd not decrease cell viability of SKBr3 cells or induce formation of acidic vesicular organelles, which corresponds to the final step of the autophagy process in this cell line. Conclusion: The effect of ICI 182,780 on increasing acidic vesicular organelles in estrogen receptor-positive breast cancer cells appears to be associated with its inhibitory effect on estrogen receptors, and GPER does notseem to be involved. Understanding these mechanisms may guide further investigations of these receptors' involvement in cellular processes of breast cancer resistance. (AU)

FAPESP's process: 13/20073-2 - Autophagy as a protective mechanism in senescent rats
Grantee:Soraya Soubhi Smaili
Support type: Regular Research Grants
FAPESP's process: 08/11515-3 - Mechanisms of Intracellular Calcium Signaling int the Modulation of Apoptosis and Autophagy
Grantee:Soraya Soubhi Smaili
Support type: Regular Research Grants