Investigating Curcumin/Intestinal Epithelium Interaction in a Millifluidic Bioreactor
Multidrug resistance is still an obstacle for chemotherapeutic treatments. One of the proteins involved in this phenomenon is the P-glycoprotein, P-gp, which is known to be responsible for the efflux of therapeutic substances from the cell cytoplasm. To date, the identification of a drug that can ef...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-08-01
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| Series: | Bioengineering |
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| Online Access: | https://www.mdpi.com/2306-5354/7/3/100 |
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| author | Joana Costa Vanessa Almonti Ludovica Cacopardo Daniele Poli Simona Rapposelli Arti Ahluwalia |
| author_facet | Joana Costa Vanessa Almonti Ludovica Cacopardo Daniele Poli Simona Rapposelli Arti Ahluwalia |
| author_sort | Joana Costa |
| collection | DOAJ |
| description | Multidrug resistance is still an obstacle for chemotherapeutic treatments. One of the proteins involved in this phenomenon is the P-glycoprotein, P-gp, which is known to be responsible for the efflux of therapeutic substances from the cell cytoplasm. To date, the identification of a drug that can efficiently inhibit P-gp activity remains a challenge, nevertheless some studies have identified natural compounds suitable for that purpose. Amongst them, curcumin has shown an inhibitory effect on the protein in in vitro studies using Caco-2 cells. To understand if flow can modulate the influence of curcumin on the protein’s activity, we studied the uptake of a P-gp substrate under static and dynamic conditions. Caco-2 cells were cultured in bioreactors and in Transwells and the basolateral transport of rhodamine-123 was assessed in the two systems as a function of the P-gp activity. Experiments were performed with and without pre-treatment of the cells with an extract of curcumin or an arylmethyloxy-phenyl derivative to evaluate the inhibitory effect of the natural substance with respect to a synthetic compound. The results indicated that the P-gp activity of the cells cultured in the bioreactors was intrinsically lower, and that the effect of both natural and synthetic inhibitors was up modulated by the presence of flow. Our study underlies the fact that the use of more sophisticated and physiologically relevant in vitro models can bring new insights on the therapeutic effects of natural substances such as curcumin. |
| first_indexed | 2024-03-10T16:48:38Z |
| format | Article |
| id | doaj.art-464db39162844f34930456955fa355c9 |
| institution | Directory Open Access Journal |
| issn | 2306-5354 |
| language | English |
| last_indexed | 2024-03-10T16:48:38Z |
| publishDate | 2020-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Bioengineering |
| spelling | doaj.art-464db39162844f34930456955fa355c92023-11-20T11:23:53ZengMDPI AGBioengineering2306-53542020-08-017310010.3390/bioengineering7030100Investigating Curcumin/Intestinal Epithelium Interaction in a Millifluidic BioreactorJoana Costa0Vanessa Almonti1Ludovica Cacopardo2Daniele Poli3Simona Rapposelli4Arti Ahluwalia5Research Center “E. Piaggio”, University of Pisa, 56122 Pisa, ItalyLARF-DIMES, Department of Experimental Medicine, University of Genoa, 16126 Genoa, ItalyResearch Center “E. Piaggio”, University of Pisa, 56122 Pisa, ItalyResearch Center “E. Piaggio”, University of Pisa, 56122 Pisa, ItalyCentro 3R (Inter-University Center for the Promotion of the 3Rs Principles in Teaching & Research), 56122 Pisa, ItalyResearch Center “E. Piaggio”, University of Pisa, 56122 Pisa, ItalyMultidrug resistance is still an obstacle for chemotherapeutic treatments. One of the proteins involved in this phenomenon is the P-glycoprotein, P-gp, which is known to be responsible for the efflux of therapeutic substances from the cell cytoplasm. To date, the identification of a drug that can efficiently inhibit P-gp activity remains a challenge, nevertheless some studies have identified natural compounds suitable for that purpose. Amongst them, curcumin has shown an inhibitory effect on the protein in in vitro studies using Caco-2 cells. To understand if flow can modulate the influence of curcumin on the protein’s activity, we studied the uptake of a P-gp substrate under static and dynamic conditions. Caco-2 cells were cultured in bioreactors and in Transwells and the basolateral transport of rhodamine-123 was assessed in the two systems as a function of the P-gp activity. Experiments were performed with and without pre-treatment of the cells with an extract of curcumin or an arylmethyloxy-phenyl derivative to evaluate the inhibitory effect of the natural substance with respect to a synthetic compound. The results indicated that the P-gp activity of the cells cultured in the bioreactors was intrinsically lower, and that the effect of both natural and synthetic inhibitors was up modulated by the presence of flow. Our study underlies the fact that the use of more sophisticated and physiologically relevant in vitro models can bring new insights on the therapeutic effects of natural substances such as curcumin.https://www.mdpi.com/2306-5354/7/3/100curcuminCaco-2 cellsfluidic systemsP-gp modulationbioreactorsintestinal in-vitro models |
| spellingShingle | Joana Costa Vanessa Almonti Ludovica Cacopardo Daniele Poli Simona Rapposelli Arti Ahluwalia Investigating Curcumin/Intestinal Epithelium Interaction in a Millifluidic Bioreactor Bioengineering curcumin Caco-2 cells fluidic systems P-gp modulation bioreactors intestinal in-vitro models |
| title | Investigating Curcumin/Intestinal Epithelium Interaction in a Millifluidic Bioreactor |
| title_full | Investigating Curcumin/Intestinal Epithelium Interaction in a Millifluidic Bioreactor |
| title_fullStr | Investigating Curcumin/Intestinal Epithelium Interaction in a Millifluidic Bioreactor |
| title_full_unstemmed | Investigating Curcumin/Intestinal Epithelium Interaction in a Millifluidic Bioreactor |
| title_short | Investigating Curcumin/Intestinal Epithelium Interaction in a Millifluidic Bioreactor |
| title_sort | investigating curcumin intestinal epithelium interaction in a millifluidic bioreactor |
| topic | curcumin Caco-2 cells fluidic systems P-gp modulation bioreactors intestinal in-vitro models |
| url | https://www.mdpi.com/2306-5354/7/3/100 |
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