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Novel Broccoli Sulforaphane-Based Analogues Inhibit the Progression of Pancreatic Cancer without Side Effects

The naturally occurring isothiocyanate sulforaphane, found in Brassicaceae vegetables, is promising in cancer treatment, e.g., by the normalization of enhanced levels of NF-κB-signaling in tumor stem cells. We chemically synthesized seven sulforaphane analogues by substitution of the sulfinyl group...

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Autores principales: Georgikou, Christina, Buglioni, Laura, Bremerich, Maximilian, Roubicek, Nico, Yin, Libo, Gross, Wolfgang, Sticht, Carsten, Bolm, Carsten, Herr, Ingrid
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7277136/
https://www.ncbi.nlm.nih.gov/pubmed/32429039
http://dx.doi.org/10.3390/biom10050769
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author Georgikou, Christina
Buglioni, Laura
Bremerich, Maximilian
Roubicek, Nico
Yin, Libo
Gross, Wolfgang
Sticht, Carsten
Bolm, Carsten
Herr, Ingrid
author_facet Georgikou, Christina
Buglioni, Laura
Bremerich, Maximilian
Roubicek, Nico
Yin, Libo
Gross, Wolfgang
Sticht, Carsten
Bolm, Carsten
Herr, Ingrid
author_sort Georgikou, Christina
collection PubMed
description The naturally occurring isothiocyanate sulforaphane, found in Brassicaceae vegetables, is promising in cancer treatment, e.g., by the normalization of enhanced levels of NF-κB-signaling in tumor stem cells. We chemically synthesized seven sulforaphane analogues by substitution of the sulfinyl group (S(O)) to either sulfimidoyl (S(NR)) or sulfonimidoyl (S (O) (NR)) groups, and characterized them in the cell lines of pancreatic cancer and several other tumor entities, including the NCI-60 cell panel. MTT and colony forming assays, flow cytometry, immunohistochemistry, microRNA arrays, bioinformatics, tumor xenotransplantation, and Kaplan Meier survival curves were performed. Compared to sulforaphane, the analogue SF102 was most efficient in inhibition of viability, colony formation, tumor growth, and the induction of apoptosis, followed by SF134. Side effects were not observed, as concluded from the body weight and liver histology of chick embryos and survival of C. elegans nematodes. Among 6659 differentially regulated microRNAs, miR29b-1-5p, and miR-27b-5p were downregulated by sulforaphane compared to controls, but upregulated by SF102 and SF134 compared to sulforaphane, suggesting differential signaling. Each substance was involved in the regulation of several NF-κB-related target genes. In conclusion, sulforaphane analogues are promising for the development of highly active new drugs in cancer treatment.
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spelling pubmed-72771362020-06-15 Novel Broccoli Sulforaphane-Based Analogues Inhibit the Progression of Pancreatic Cancer without Side Effects Georgikou, Christina Buglioni, Laura Bremerich, Maximilian Roubicek, Nico Yin, Libo Gross, Wolfgang Sticht, Carsten Bolm, Carsten Herr, Ingrid Biomolecules Article The naturally occurring isothiocyanate sulforaphane, found in Brassicaceae vegetables, is promising in cancer treatment, e.g., by the normalization of enhanced levels of NF-κB-signaling in tumor stem cells. We chemically synthesized seven sulforaphane analogues by substitution of the sulfinyl group (S(O)) to either sulfimidoyl (S(NR)) or sulfonimidoyl (S (O) (NR)) groups, and characterized them in the cell lines of pancreatic cancer and several other tumor entities, including the NCI-60 cell panel. MTT and colony forming assays, flow cytometry, immunohistochemistry, microRNA arrays, bioinformatics, tumor xenotransplantation, and Kaplan Meier survival curves were performed. Compared to sulforaphane, the analogue SF102 was most efficient in inhibition of viability, colony formation, tumor growth, and the induction of apoptosis, followed by SF134. Side effects were not observed, as concluded from the body weight and liver histology of chick embryos and survival of C. elegans nematodes. Among 6659 differentially regulated microRNAs, miR29b-1-5p, and miR-27b-5p were downregulated by sulforaphane compared to controls, but upregulated by SF102 and SF134 compared to sulforaphane, suggesting differential signaling. Each substance was involved in the regulation of several NF-κB-related target genes. In conclusion, sulforaphane analogues are promising for the development of highly active new drugs in cancer treatment. MDPI 2020-05-15 /pmc/articles/PMC7277136/ /pubmed/32429039 http://dx.doi.org/10.3390/biom10050769 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Georgikou, Christina
Buglioni, Laura
Bremerich, Maximilian
Roubicek, Nico
Yin, Libo
Gross, Wolfgang
Sticht, Carsten
Bolm, Carsten
Herr, Ingrid
Novel Broccoli Sulforaphane-Based Analogues Inhibit the Progression of Pancreatic Cancer without Side Effects
title Novel Broccoli Sulforaphane-Based Analogues Inhibit the Progression of Pancreatic Cancer without Side Effects
title_full Novel Broccoli Sulforaphane-Based Analogues Inhibit the Progression of Pancreatic Cancer without Side Effects
title_fullStr Novel Broccoli Sulforaphane-Based Analogues Inhibit the Progression of Pancreatic Cancer without Side Effects
title_full_unstemmed Novel Broccoli Sulforaphane-Based Analogues Inhibit the Progression of Pancreatic Cancer without Side Effects
title_short Novel Broccoli Sulforaphane-Based Analogues Inhibit the Progression of Pancreatic Cancer without Side Effects
title_sort novel broccoli sulforaphane-based analogues inhibit the progression of pancreatic cancer without side effects
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7277136/
https://www.ncbi.nlm.nih.gov/pubmed/32429039
http://dx.doi.org/10.3390/biom10050769
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