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

Research

Yuniel Fernandez-Marrero¹  Luc H. Boudreau²  Mathieu P. A. Hébert²  Narjara Gonzalez Suarez³  Borhane Annabi³  Marie-Eve Roy³ 

[1] Cell Biology Department, NuChem Sciences, H4R 2N6, Montreal, QC, Canada;Department of Chemistry and Biochemistry, Université de Moncton and New Brunswick Center for Precision Medicine, Moncton, NB, Canada;Laboratoire d’Oncologie Moléculaire, Département de Chimie, Université du Québec À Montréal and CERMO-FC, C.P. 8888, Succ. Centre-Ville, H3C 3P8, Montreal, QC, Canada;

关键词: EGCG;    Triple-negative breast cancer;    Extracellular vesicles;    Adipose-derived mesenchymal stem cells;    Inflammation;    Senescence;   

DOI  :  10.1186/s12935-023-03087-2

 received in 2023-06-20, accepted in 2023-09-29,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundTriple-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.MethodsEVs 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.ResultsWhile 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.ConclusionThis 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.

【 授权许可】

CC BY   
© BioMed Central Ltd., part of Springer Nature 2023

【 图 表 】

Fig. 3

Fig. 3

42004_2023_1020_Article_IEq18.gif

Fig. 3

Fig. 2

12951_2017_315_Article_IEq1.gif

Fig. 2

Fig. 8

Fig. 4

40517_2023_273_Article_IEq6.gif

Fig. 3