Pseudoalteromonas haloplanktis TAC125 produces 4-hydroxybenzoic acid that induces pyroptosis in human A459 lung adenocarcinoma cells

Abstract In order to exploit the rich reservoir of marine cold-adapted bacteria as a source of bioactive metabolites, ethyl acetate crude extracts of thirteen polar marine bacteria were tested for their antiproliferative activity on A549 lung epithelial cancer cells. The crude extract from Pseudoalt...

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Autores principales:	Filomena Sannino, Clementina Sansone, Christian Galasso, Sara Kildgaard, Pietro Tedesco, Renato Fani, Gennaro Marino, Donatella de Pascale, Adrianna Ianora, Ermenegilda Parrilli, Thomas Ostenfeld Larsen, Giovanna Romano, Maria Luisa Tutino
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f275cb7865a8426a9d4b8b5f44f7bc5c
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spelling	oai:doaj.org-article:f275cb7865a8426a9d4b8b5f44f7bc5c2021-12-02T15:08:07ZPseudoalteromonas haloplanktis TAC125 produces 4-hydroxybenzoic acid that induces pyroptosis in human A459 lung adenocarcinoma cells10.1038/s41598-018-19536-22045-2322https://doaj.org/article/f275cb7865a8426a9d4b8b5f44f7bc5c2018-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-19536-2https://doaj.org/toc/2045-2322Abstract In order to exploit the rich reservoir of marine cold-adapted bacteria as a source of bioactive metabolites, ethyl acetate crude extracts of thirteen polar marine bacteria were tested for their antiproliferative activity on A549 lung epithelial cancer cells. The crude extract from Pseudoalteromonas haloplanktis TAC125 was the most active in inhibiting cell proliferation. Extensive bioassay-guided purification and mass spectrometric characterization allowed the identification of 4-hydroxybenzoic acid (4-HBA) as the molecule responsible for this bioactivity. We further demonstrate that 4-HBA inhibits A549 cancer cell proliferation with an IC50 value ≤ 1 μg ml−1, and that the effect is specific, since the other two HBA isomers (i.e. 2-HBA and 3-HBA) were unable to inhibit cell proliferation. The effect of 4-HBA is also selective since treatment of normal lung epithelial cells (WI-38) with 4-HBA did not affect cell viability. Finally, we show that 4-HBA is able to activate, at the gene and protein levels, a specific cell death signaling pathway named pyroptosis. Accordingly, the treatment of A549 cells with 4-HBA induces the transcription of (amongst others) caspase-1, IL1β, and IL18 encoding genes. Studies needed for the elucidation of mode of action of 4-HBA will be instrumental in depicting novel details of pyroptosis.Filomena SanninoClementina SansoneChristian GalassoSara KildgaardPietro TedescoRenato FaniGennaro MarinoDonatella de PascaleAdrianna IanoraErmenegilda ParrilliThomas Ostenfeld LarsenGiovanna RomanoMaria Luisa TutinoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-10 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Filomena Sannino Clementina Sansone Christian Galasso Sara Kildgaard Pietro Tedesco Renato Fani Gennaro Marino Donatella de Pascale Adrianna Ianora Ermenegilda Parrilli Thomas Ostenfeld Larsen Giovanna Romano Maria Luisa Tutino Pseudoalteromonas haloplanktis TAC125 produces 4-hydroxybenzoic acid that induces pyroptosis in human A459 lung adenocarcinoma cells
description	Abstract In order to exploit the rich reservoir of marine cold-adapted bacteria as a source of bioactive metabolites, ethyl acetate crude extracts of thirteen polar marine bacteria were tested for their antiproliferative activity on A549 lung epithelial cancer cells. The crude extract from Pseudoalteromonas haloplanktis TAC125 was the most active in inhibiting cell proliferation. Extensive bioassay-guided purification and mass spectrometric characterization allowed the identification of 4-hydroxybenzoic acid (4-HBA) as the molecule responsible for this bioactivity. We further demonstrate that 4-HBA inhibits A549 cancer cell proliferation with an IC50 value ≤ 1 μg ml−1, and that the effect is specific, since the other two HBA isomers (i.e. 2-HBA and 3-HBA) were unable to inhibit cell proliferation. The effect of 4-HBA is also selective since treatment of normal lung epithelial cells (WI-38) with 4-HBA did not affect cell viability. Finally, we show that 4-HBA is able to activate, at the gene and protein levels, a specific cell death signaling pathway named pyroptosis. Accordingly, the treatment of A549 cells with 4-HBA induces the transcription of (amongst others) caspase-1, IL1β, and IL18 encoding genes. Studies needed for the elucidation of mode of action of 4-HBA will be instrumental in depicting novel details of pyroptosis.
format	article
author	Filomena Sannino Clementina Sansone Christian Galasso Sara Kildgaard Pietro Tedesco Renato Fani Gennaro Marino Donatella de Pascale Adrianna Ianora Ermenegilda Parrilli Thomas Ostenfeld Larsen Giovanna Romano Maria Luisa Tutino
author_facet	Filomena Sannino Clementina Sansone Christian Galasso Sara Kildgaard Pietro Tedesco Renato Fani Gennaro Marino Donatella de Pascale Adrianna Ianora Ermenegilda Parrilli Thomas Ostenfeld Larsen Giovanna Romano Maria Luisa Tutino
author_sort	Filomena Sannino
title	Pseudoalteromonas haloplanktis TAC125 produces 4-hydroxybenzoic acid that induces pyroptosis in human A459 lung adenocarcinoma cells
title_short	Pseudoalteromonas haloplanktis TAC125 produces 4-hydroxybenzoic acid that induces pyroptosis in human A459 lung adenocarcinoma cells
title_full	Pseudoalteromonas haloplanktis TAC125 produces 4-hydroxybenzoic acid that induces pyroptosis in human A459 lung adenocarcinoma cells
title_fullStr	Pseudoalteromonas haloplanktis TAC125 produces 4-hydroxybenzoic acid that induces pyroptosis in human A459 lung adenocarcinoma cells
title_full_unstemmed	Pseudoalteromonas haloplanktis TAC125 produces 4-hydroxybenzoic acid that induces pyroptosis in human A459 lung adenocarcinoma cells
title_sort	pseudoalteromonas haloplanktis tac125 produces 4-hydroxybenzoic acid that induces pyroptosis in human a459 lung adenocarcinoma cells
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/f275cb7865a8426a9d4b8b5f44f7bc5c
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Pseudoalteromonas haloplanktis TAC125 produces 4-hydroxybenzoic acid that induces pyroptosis in human A459 lung adenocarcinoma cells

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