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Spongiatriol Inhibits Nuclear Factor Kappa B Activation and Induces Apoptosis in Pancreatic Cancer Cells

Pancreatic cancer, the fourth leading cause of cancer death in the US, is highly resistant to all current chemotherapies, and its growth is facilitated by chronic inflammation. The majority of pro-inflammatory cytokines initiate signaling cascades that converge at the activation of the Nuclear Facto...

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Autores principales: Guzmán, Esther, Maher, Michael, Temkin, Alexis, Pitts, Tara, Wright, Amy
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3705394/
https://www.ncbi.nlm.nih.gov/pubmed/23549285
http://dx.doi.org/10.3390/md11041140
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author Guzmán, Esther
Maher, Michael
Temkin, Alexis
Pitts, Tara
Wright, Amy
author_facet Guzmán, Esther
Maher, Michael
Temkin, Alexis
Pitts, Tara
Wright, Amy
author_sort Guzmán, Esther
collection PubMed
description Pancreatic cancer, the fourth leading cause of cancer death in the US, is highly resistant to all current chemotherapies, and its growth is facilitated by chronic inflammation. The majority of pro-inflammatory cytokines initiate signaling cascades that converge at the activation of the Nuclear Factor Kappa B (NFκB), a signal transduction molecule that promotes cell survival, proliferation and angiogenesis. In an effort to identify novel inhibitors of NFκB, the HBOI library of pure compounds was screened using a reporter cell line that produces luciferin under the transcriptional control of NFκB. Seven compounds were identified through this screen, but in the case of five of them, their reported mechanism of action made them unlikely to be specific NFκB inhibitors. Spongiatriol, a marine furanoditerpenoid that was first isolated in the 1970s, is shown here to inhibit NFκB transcriptional activity in a reporter cell line, to reduce levels of phosphorylated (active) NFκB in the AsPC-1 cell line, to have an IC(50) for cytotoxicity in the low micromolar range against the AsPC-1, BxPC-3, MiaPaCa-2 and Panc-1 pancreatic cancer cell lines, and to induce moderate but significant apoptosis in both the AsPC-1 and the Panc-1 cell lines.
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spelling pubmed-37053942013-07-09 Spongiatriol Inhibits Nuclear Factor Kappa B Activation and Induces Apoptosis in Pancreatic Cancer Cells Guzmán, Esther Maher, Michael Temkin, Alexis Pitts, Tara Wright, Amy Mar Drugs Article Pancreatic cancer, the fourth leading cause of cancer death in the US, is highly resistant to all current chemotherapies, and its growth is facilitated by chronic inflammation. The majority of pro-inflammatory cytokines initiate signaling cascades that converge at the activation of the Nuclear Factor Kappa B (NFκB), a signal transduction molecule that promotes cell survival, proliferation and angiogenesis. In an effort to identify novel inhibitors of NFκB, the HBOI library of pure compounds was screened using a reporter cell line that produces luciferin under the transcriptional control of NFκB. Seven compounds were identified through this screen, but in the case of five of them, their reported mechanism of action made them unlikely to be specific NFκB inhibitors. Spongiatriol, a marine furanoditerpenoid that was first isolated in the 1970s, is shown here to inhibit NFκB transcriptional activity in a reporter cell line, to reduce levels of phosphorylated (active) NFκB in the AsPC-1 cell line, to have an IC(50) for cytotoxicity in the low micromolar range against the AsPC-1, BxPC-3, MiaPaCa-2 and Panc-1 pancreatic cancer cell lines, and to induce moderate but significant apoptosis in both the AsPC-1 and the Panc-1 cell lines. MDPI 2013-04-02 /pmc/articles/PMC3705394/ /pubmed/23549285 http://dx.doi.org/10.3390/md11041140 Text en © 2013 by the authors; licensee MDPI, Basel, Switzerland. http://creativecommons.org/licenses/by/3.0/ This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).
spellingShingle Article
Guzmán, Esther
Maher, Michael
Temkin, Alexis
Pitts, Tara
Wright, Amy
Spongiatriol Inhibits Nuclear Factor Kappa B Activation and Induces Apoptosis in Pancreatic Cancer Cells
title Spongiatriol Inhibits Nuclear Factor Kappa B Activation and Induces Apoptosis in Pancreatic Cancer Cells
title_full Spongiatriol Inhibits Nuclear Factor Kappa B Activation and Induces Apoptosis in Pancreatic Cancer Cells
title_fullStr Spongiatriol Inhibits Nuclear Factor Kappa B Activation and Induces Apoptosis in Pancreatic Cancer Cells
title_full_unstemmed Spongiatriol Inhibits Nuclear Factor Kappa B Activation and Induces Apoptosis in Pancreatic Cancer Cells
title_short Spongiatriol Inhibits Nuclear Factor Kappa B Activation and Induces Apoptosis in Pancreatic Cancer Cells
title_sort spongiatriol inhibits nuclear factor kappa b activation and induces apoptosis in pancreatic cancer cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3705394/
https://www.ncbi.nlm.nih.gov/pubmed/23549285
http://dx.doi.org/10.3390/md11041140
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