TY - JOUR
T1 - Curcumin modulates chronic myelogenous leukemia exosomes composition and affects angiogenic phenotype, via exosomal miR-21
AU - Taverna, Simona
AU - Fontana, Simona
AU - De Leo, Giacomo
AU - De Caro, Viviana
AU - Monteleone, Francesca
AU - Pucci, Marzia
AU - Vicario, Emanuela
AU - Saieva, Laura
AU - Giallombardo, Marco
AU - Alessandro, Riccardo
AU - Rolfo, Christian
PY - 2016
Y1 - 2016
N2 - Tumor derived exosomes are vesicles which contain proteins and microRNAs that mediate cell-cell communication and are involved in angiogenesis and tumor progression. Curcumin derived from the plant Curcuma longa, shows anticancer effects. Exosomes released by CML cells treated with Curcumin contain a high amount of miR-21 that is shuttled into the endothelial cells in a biologically active form. The treatment of HUVECs with CML Curcu-exosomes reduced RhoB expression and negatively modulated endothelial cells motility. We showed that the addition of CML control exosomes to HUVECs caused an increase in IL8 and VCAM1 levels, but Curcu- exosomes reversed these effects thus attenuating their angiogenic properties. This in vitro and in vivo vascular network revealed that Curcumin treatment deeply changes their molecular properties, in particular, Curcumin induces a release of exosomes depleted in pro-angiogenic proteins and enriched in proteins endowed with anti-angiogenic activity. Among the proteins differential expressed we focused on MARCKS, since it was the most modulated protein and a target of miR-21. Taken together our data indicated that also Curcumin attenuates the exosome’s ability to promote the angiogenic phenotype and to modulate the endothelial barrier organization
AB - Tumor derived exosomes are vesicles which contain proteins and microRNAs that mediate cell-cell communication and are involved in angiogenesis and tumor progression. Curcumin derived from the plant Curcuma longa, shows anticancer effects. Exosomes released by CML cells treated with Curcumin contain a high amount of miR-21 that is shuttled into the endothelial cells in a biologically active form. The treatment of HUVECs with CML Curcu-exosomes reduced RhoB expression and negatively modulated endothelial cells motility. We showed that the addition of CML control exosomes to HUVECs caused an increase in IL8 and VCAM1 levels, but Curcu- exosomes reversed these effects thus attenuating their angiogenic properties. This in vitro and in vivo vascular network revealed that Curcumin treatment deeply changes their molecular properties, in particular, Curcumin induces a release of exosomes depleted in pro-angiogenic proteins and enriched in proteins endowed with anti-angiogenic activity. Among the proteins differential expressed we focused on MARCKS, since it was the most modulated protein and a target of miR-21. Taken together our data indicated that also Curcumin attenuates the exosome’s ability to promote the angiogenic phenotype and to modulate the endothelial barrier organization
UR - http://hdl.handle.net/10447/176116
M3 - Article
VL - 7
SP - 30420
EP - 30439
JO - Oncotarget
JF - Oncotarget
SN - 1949-2553
ER -