EGCG inhibits the inflammation and senescence inducing properties of MDA-MB-231 triple-negative breast cancer (TNBC) cells-derived extracellular vesicles in human adipose-derived mesenchymal stem cells
Abstract Background Triple-negative breast cancer (TNBC) cells’ secretome can induce a pro-inflammatory phenotype in human adipose-derived mesenchymal stem cells (hADMSC). This can be prevented by the green tea polyphenol epigallocatechin-3-gallate (EGCG). The impact of EGCG on the paracrine regulat...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-10-01
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| Series: | Cancer Cell International |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12935-023-03087-2 |
| _version_ | 1797451414306291712 |
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| author | Narjara Gonzalez Suarez Yuniel Fernandez-Marrero Mathieu P. A. Hébert Marie-Eve Roy Luc H. Boudreau Borhane Annabi |
| author_facet | Narjara Gonzalez Suarez Yuniel Fernandez-Marrero Mathieu P. A. Hébert Marie-Eve Roy Luc H. Boudreau Borhane Annabi |
| author_sort | Narjara Gonzalez Suarez |
| collection | DOAJ |
| description | Abstract Background Triple-negative breast cancer (TNBC) cells’ secretome can induce a pro-inflammatory phenotype in human adipose-derived mesenchymal stem cells (hADMSC). This can be prevented by the green tea polyphenol epigallocatechin-3-gallate (EGCG). The impact of EGCG on the paracrine regulation that the extracellular vesicles (EVs) specifically exert within the TNBC secretome remains unknown. Methods EVs were obtained from a TNBC-derived serum-starved MDA-MB-231 cell model treated or not with EGCG under normoxic or hypoxic (< 1% O2) culture conditions. RNA-Seq analysis was used to assess the EVs’ genetic content. The modulation of inflammatory and senescence markers in hADMSC was evaluated by RT-qPCR using cDNA arrays and validated by immunoblotting. A protein profiler phospho-kinase array was used to explore signaling pathways. Results While hypoxic culture conditions did not significantly alter the genetic content of MDA-MB-231-secreted EVs, the addition of EGCG significantly modified EVs genetic material at low oxygen tension. Gene expression of cancer-associated adipocyte pro-inflammatory markers CXCL8, CCL2 and IL-1β was increased in hADMSC treated with EVs. Concomitantly, EVs isolated from MDA-MB-231 treated with EGCG (EGCG-EVs) downregulated CCL2 and IL-1β, while inducing higher expression of CXCL8 and IL-6 levels. EVs activated CHK-2, c-Jun, AKT and GSK-3β signaling pathways in hADMSC, whereas EGCG-EVs specifically reduced the latter two as well as the serum starvation-induced senescence markers p21 and β-galactosidase. Finally, the mitochondrial content within the TNBC cells-derived EVs was found reduced upon EGCG treatment. Conclusion This proof of concept study demonstrates that the chemopreventive properties of diet-derived polyphenols may efficiently target the paracrine regulation that TNBC cells could exert upon their surrounding adipose tissue microenvironment. |
| first_indexed | 2024-03-09T14:54:20Z |
| format | Article |
| id | doaj.art-894527d53da14376b871eeea5f6fc51e |
| institution | Directory Open Access Journal |
| issn | 1475-2867 |
| language | English |
| last_indexed | 2024-03-09T14:54:20Z |
| publishDate | 2023-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Cancer Cell International |
| spelling | doaj.art-894527d53da14376b871eeea5f6fc51e2023-11-26T14:18:23ZengBMCCancer Cell International1475-28672023-10-0123112110.1186/s12935-023-03087-2EGCG inhibits the inflammation and senescence inducing properties of MDA-MB-231 triple-negative breast cancer (TNBC) cells-derived extracellular vesicles in human adipose-derived mesenchymal stem cellsNarjara Gonzalez Suarez0Yuniel Fernandez-Marrero1Mathieu P. A. Hébert2Marie-Eve Roy3Luc H. Boudreau4Borhane Annabi5Laboratoire d’Oncologie Moléculaire, Département de Chimie, Université du Québec À Montréal and CERMO-FCCell Biology Department, NuChem SciencesDepartment of Chemistry and Biochemistry, Université de Moncton and New Brunswick Center for Precision MedicineLaboratoire d’Oncologie Moléculaire, Département de Chimie, Université du Québec À Montréal and CERMO-FCDepartment of Chemistry and Biochemistry, Université de Moncton and New Brunswick Center for Precision MedicineLaboratoire d’Oncologie Moléculaire, Département de Chimie, Université du Québec À Montréal and CERMO-FCAbstract Background Triple-negative breast cancer (TNBC) cells’ secretome can induce a pro-inflammatory phenotype in human adipose-derived mesenchymal stem cells (hADMSC). This can be prevented by the green tea polyphenol epigallocatechin-3-gallate (EGCG). The impact of EGCG on the paracrine regulation that the extracellular vesicles (EVs) specifically exert within the TNBC secretome remains unknown. Methods EVs were obtained from a TNBC-derived serum-starved MDA-MB-231 cell model treated or not with EGCG under normoxic or hypoxic (< 1% O2) culture conditions. RNA-Seq analysis was used to assess the EVs’ genetic content. The modulation of inflammatory and senescence markers in hADMSC was evaluated by RT-qPCR using cDNA arrays and validated by immunoblotting. A protein profiler phospho-kinase array was used to explore signaling pathways. Results While hypoxic culture conditions did not significantly alter the genetic content of MDA-MB-231-secreted EVs, the addition of EGCG significantly modified EVs genetic material at low oxygen tension. Gene expression of cancer-associated adipocyte pro-inflammatory markers CXCL8, CCL2 and IL-1β was increased in hADMSC treated with EVs. Concomitantly, EVs isolated from MDA-MB-231 treated with EGCG (EGCG-EVs) downregulated CCL2 and IL-1β, while inducing higher expression of CXCL8 and IL-6 levels. EVs activated CHK-2, c-Jun, AKT and GSK-3β signaling pathways in hADMSC, whereas EGCG-EVs specifically reduced the latter two as well as the serum starvation-induced senescence markers p21 and β-galactosidase. Finally, the mitochondrial content within the TNBC cells-derived EVs was found reduced upon EGCG treatment. Conclusion This proof of concept study demonstrates that the chemopreventive properties of diet-derived polyphenols may efficiently target the paracrine regulation that TNBC cells could exert upon their surrounding adipose tissue microenvironment.https://doi.org/10.1186/s12935-023-03087-2EGCGTriple-negative breast cancerExtracellular vesiclesAdipose-derived mesenchymal stem cellsInflammationSenescence |
| spellingShingle | Narjara Gonzalez Suarez Yuniel Fernandez-Marrero Mathieu P. A. Hébert Marie-Eve Roy Luc H. Boudreau Borhane Annabi EGCG inhibits the inflammation and senescence inducing properties of MDA-MB-231 triple-negative breast cancer (TNBC) cells-derived extracellular vesicles in human adipose-derived mesenchymal stem cells Cancer Cell International EGCG Triple-negative breast cancer Extracellular vesicles Adipose-derived mesenchymal stem cells Inflammation Senescence |
| title | EGCG inhibits the inflammation and senescence inducing properties of MDA-MB-231 triple-negative breast cancer (TNBC) cells-derived extracellular vesicles in human adipose-derived mesenchymal stem cells |
| title_full | EGCG inhibits the inflammation and senescence inducing properties of MDA-MB-231 triple-negative breast cancer (TNBC) cells-derived extracellular vesicles in human adipose-derived mesenchymal stem cells |
| title_fullStr | EGCG inhibits the inflammation and senescence inducing properties of MDA-MB-231 triple-negative breast cancer (TNBC) cells-derived extracellular vesicles in human adipose-derived mesenchymal stem cells |
| title_full_unstemmed | EGCG inhibits the inflammation and senescence inducing properties of MDA-MB-231 triple-negative breast cancer (TNBC) cells-derived extracellular vesicles in human adipose-derived mesenchymal stem cells |
| title_short | EGCG inhibits the inflammation and senescence inducing properties of MDA-MB-231 triple-negative breast cancer (TNBC) cells-derived extracellular vesicles in human adipose-derived mesenchymal stem cells |
| title_sort | egcg inhibits the inflammation and senescence inducing properties of mda mb 231 triple negative breast cancer tnbc cells derived extracellular vesicles in human adipose derived mesenchymal stem cells |
| topic | EGCG Triple-negative breast cancer Extracellular vesicles Adipose-derived mesenchymal stem cells Inflammation Senescence |
| url | https://doi.org/10.1186/s12935-023-03087-2 |
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