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A novel purified Lactobacillus acidophilus 20079 exopolysaccharide, LA-EPS-20079, molecularly regulates both apoptotic and NF-κB inflammatory pathways in human colon cancer

BACKGROUND: The direct link between inflammatory bowel diseases and colorectal cancer is well documented. Previous studies have reported that some lactic acid bacterial strains could inhibit colon cancer progression however; the exact molecules involved have not yet been identified. So, in the curre...

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Autores principales: El-Deeb, Nehal M., Yassin, Abdelrahman M., Al-Madboly, Lamiaa A., El-Hawiet, Amr
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5820793/
https://www.ncbi.nlm.nih.gov/pubmed/29466981
http://dx.doi.org/10.1186/s12934-018-0877-z
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author El-Deeb, Nehal M.
Yassin, Abdelrahman M.
Al-Madboly, Lamiaa A.
El-Hawiet, Amr
author_facet El-Deeb, Nehal M.
Yassin, Abdelrahman M.
Al-Madboly, Lamiaa A.
El-Hawiet, Amr
author_sort El-Deeb, Nehal M.
collection PubMed
description BACKGROUND: The direct link between inflammatory bowel diseases and colorectal cancer is well documented. Previous studies have reported that some lactic acid bacterial strains could inhibit colon cancer progression however; the exact molecules involved have not yet been identified. So, in the current study, we illustrated the tumor suppressive effects of the newly identified Lactobacillus acidophilus DSMZ 20079 cell-free pentasaccharide against colon cancer cells. The chemical structure of the purified pentasaccharide was investigated by MALDI-TOF mass spectrum, 1D and 2D Nuclear Magnetic Resonance (NMR). The anticancer potentiality of the purified pentasaccharide against both Human colon cancer (CaCo-2) and Human breast cancer (MCF7) cell lines with its safety usage pattern were evaluated using cytotoxicity, annexin V quantification and BrdU incorporation assays. Also, the immunomodulatory effects of the identified compound were quantified on both LPS-induced PBMC cell model and cancer cells with monitoring the immunophenotyping of T and dendritic cell surface marker. At molecular level, the alteration in gene expression of both inflammatory and apoptotic pathways were quantified upon pentasaccharide-cellular treatment by RTqPCR. RESULTS: The obtained data of the spectroscopic analysis, confirmed the structure of the newly extracted pentasaccharide; (LA-EPS-20079) to be: α-d-Glc (1→2)][α-l-Fuc(1→4)] α-d-GlcA(1→2) α-d-GlcA(1→2) α-d-GlcA. This pentasaccharide, recorded safe dose on normal mammalian cells ranged from 2 to 5 mg/ml with cancer cells selectivity index, ranged of 1.96–51.3. Upon CaCo-2 cell treatment with the non-toxic dose of LA-EPS-20079, the inhibition percentage in CaCo-2 cellular viability, reached 80.65 with an increase in the ratio of the apoptotic cells in sub-G0/G1 cell cycle phase. Also, this pentasaccharide showed potentialities to up-regulate the expression of IKbα, P53 and TGF genes. CONCLUSION: The anticancer potentialities of LA-EPS-20079 oligosaccharides against human colon cancer represented through its regulatory effects on both apoptotic and NF-κB inflammatory pathways. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12934-018-0877-z) contains supplementary material, which is available to authorized users.
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spelling pubmed-58207932018-02-26 A novel purified Lactobacillus acidophilus 20079 exopolysaccharide, LA-EPS-20079, molecularly regulates both apoptotic and NF-κB inflammatory pathways in human colon cancer El-Deeb, Nehal M. Yassin, Abdelrahman M. Al-Madboly, Lamiaa A. El-Hawiet, Amr Microb Cell Fact Research BACKGROUND: The direct link between inflammatory bowel diseases and colorectal cancer is well documented. Previous studies have reported that some lactic acid bacterial strains could inhibit colon cancer progression however; the exact molecules involved have not yet been identified. So, in the current study, we illustrated the tumor suppressive effects of the newly identified Lactobacillus acidophilus DSMZ 20079 cell-free pentasaccharide against colon cancer cells. The chemical structure of the purified pentasaccharide was investigated by MALDI-TOF mass spectrum, 1D and 2D Nuclear Magnetic Resonance (NMR). The anticancer potentiality of the purified pentasaccharide against both Human colon cancer (CaCo-2) and Human breast cancer (MCF7) cell lines with its safety usage pattern were evaluated using cytotoxicity, annexin V quantification and BrdU incorporation assays. Also, the immunomodulatory effects of the identified compound were quantified on both LPS-induced PBMC cell model and cancer cells with monitoring the immunophenotyping of T and dendritic cell surface marker. At molecular level, the alteration in gene expression of both inflammatory and apoptotic pathways were quantified upon pentasaccharide-cellular treatment by RTqPCR. RESULTS: The obtained data of the spectroscopic analysis, confirmed the structure of the newly extracted pentasaccharide; (LA-EPS-20079) to be: α-d-Glc (1→2)][α-l-Fuc(1→4)] α-d-GlcA(1→2) α-d-GlcA(1→2) α-d-GlcA. This pentasaccharide, recorded safe dose on normal mammalian cells ranged from 2 to 5 mg/ml with cancer cells selectivity index, ranged of 1.96–51.3. Upon CaCo-2 cell treatment with the non-toxic dose of LA-EPS-20079, the inhibition percentage in CaCo-2 cellular viability, reached 80.65 with an increase in the ratio of the apoptotic cells in sub-G0/G1 cell cycle phase. Also, this pentasaccharide showed potentialities to up-regulate the expression of IKbα, P53 and TGF genes. CONCLUSION: The anticancer potentialities of LA-EPS-20079 oligosaccharides against human colon cancer represented through its regulatory effects on both apoptotic and NF-κB inflammatory pathways. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12934-018-0877-z) contains supplementary material, which is available to authorized users. BioMed Central 2018-02-21 /pmc/articles/PMC5820793/ /pubmed/29466981 http://dx.doi.org/10.1186/s12934-018-0877-z Text en © The Author(s) 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
El-Deeb, Nehal M.
Yassin, Abdelrahman M.
Al-Madboly, Lamiaa A.
El-Hawiet, Amr
A novel purified Lactobacillus acidophilus 20079 exopolysaccharide, LA-EPS-20079, molecularly regulates both apoptotic and NF-κB inflammatory pathways in human colon cancer
title A novel purified Lactobacillus acidophilus 20079 exopolysaccharide, LA-EPS-20079, molecularly regulates both apoptotic and NF-κB inflammatory pathways in human colon cancer
title_full A novel purified Lactobacillus acidophilus 20079 exopolysaccharide, LA-EPS-20079, molecularly regulates both apoptotic and NF-κB inflammatory pathways in human colon cancer
title_fullStr A novel purified Lactobacillus acidophilus 20079 exopolysaccharide, LA-EPS-20079, molecularly regulates both apoptotic and NF-κB inflammatory pathways in human colon cancer
title_full_unstemmed A novel purified Lactobacillus acidophilus 20079 exopolysaccharide, LA-EPS-20079, molecularly regulates both apoptotic and NF-κB inflammatory pathways in human colon cancer
title_short A novel purified Lactobacillus acidophilus 20079 exopolysaccharide, LA-EPS-20079, molecularly regulates both apoptotic and NF-κB inflammatory pathways in human colon cancer
title_sort novel purified lactobacillus acidophilus 20079 exopolysaccharide, la-eps-20079, molecularly regulates both apoptotic and nf-κb inflammatory pathways in human colon cancer
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5820793/
https://www.ncbi.nlm.nih.gov/pubmed/29466981
http://dx.doi.org/10.1186/s12934-018-0877-z
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