A novel purified Lactobacillus acidophilus 20079 exopolysaccharide, LA-EPS-20079, molecularly regulates both apoptotic and NF-κB inflammatory pathways in human colon cancer
Abstract 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 t...
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| Format: | Article |
| Language: | English |
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BMC
2018-02-01
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| Series: | Microbial Cell Factories |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12934-018-0877-z |
| _version_ | 1819099906222063616 |
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| author | Nehal M. El-Deeb Abdelrahman M. Yassin Lamiaa A. Al-Madboly Amr El-Hawiet |
| author_facet | Nehal M. El-Deeb Abdelrahman M. Yassin Lamiaa A. Al-Madboly Amr El-Hawiet |
| author_sort | Nehal M. El-Deeb |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-12-22T00:54:19Z |
| format | Article |
| id | doaj.art-4dda9c48d00d477a8b42b20ec3dd3c13 |
| institution | Directory Open Access Journal |
| issn | 1475-2859 |
| language | English |
| last_indexed | 2024-12-22T00:54:19Z |
| publishDate | 2018-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Microbial Cell Factories |
| spelling | doaj.art-4dda9c48d00d477a8b42b20ec3dd3c132022-12-21T18:44:22ZengBMCMicrobial Cell Factories1475-28592018-02-0117111510.1186/s12934-018-0877-zA novel purified Lactobacillus acidophilus 20079 exopolysaccharide, LA-EPS-20079, molecularly regulates both apoptotic and NF-κB inflammatory pathways in human colon cancerNehal M. El-Deeb0Abdelrahman M. Yassin1Lamiaa A. Al-Madboly2Amr El-Hawiet3Biopharmacetical Product Research Department, Genetic Engineering and Biotechnology Research Institute, City of Scientific Research and Technology ApplicationsBiopharmacetical Product Research Department, Genetic Engineering and Biotechnology Research Institute, City of Scientific Research and Technology ApplicationsDepartment of Pharmaceutical Microbiology, Faculty of Pharmacy, Tanta UniversityDepartment of Pharmacognosy, Faculty of Pharmacy, Alexandria UniversityAbstract 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.http://link.springer.com/article/10.1186/s12934-018-0877-zLABNFκB pathwayOligosaccharidesT cells immunophenotypingColon cancer |
| spellingShingle | Nehal M. El-Deeb Abdelrahman M. Yassin Lamiaa A. Al-Madboly Amr El-Hawiet A novel purified Lactobacillus acidophilus 20079 exopolysaccharide, LA-EPS-20079, molecularly regulates both apoptotic and NF-κB inflammatory pathways in human colon cancer Microbial Cell Factories LAB NFκB pathway Oligosaccharides T cells immunophenotyping 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 | LAB NFκB pathway Oligosaccharides T cells immunophenotyping Colon cancer |
| url | http://link.springer.com/article/10.1186/s12934-018-0877-z |
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