TY - JOUR
T1 - Exosomes released from U87 glioma cells treated with curcumin and/or temozolomide produce apoptosis in naive U87 cells
AU - Mousavi, Seyed Mojtaba
AU - Hosseindoost, Saereh
AU - Mahdian, Seyed Mohammad Amin
AU - Vousooghi, Nasim
AU - Rajabi, Ali
AU - Jafari, Ameneh
AU - Ostadian, Amirreza
AU - Hamblin, Michael R.
AU - Hadjighassem, Mahmoud Reza
AU - Mirzaei, Hamed
N1 - Publisher Copyright:
© 2023 Elsevier GmbH
PY - 2023/5
Y1 - 2023/5
N2 - Glioblastoma (GBM) remains the most lethal brain tumor without any curative treatment. Exosomes can mediate cell-to-cell communication, and may function as a new type of targeted therapy. In this study, the therapeutic benefits of exosomes generated by U87 cells treated with curcumin and/or temozolomide were investigated. The cells were cultured and treated with temozolomide (TMZ), curcumin (Cur), or their combination (TMZ+Cur). Exosomes were isolated with a centrifugation kit and characterized using DLS, SEM, TEM, and Western blotting. The levels of exosomal BDNF and TNF-α were measured. Naïve U87 cells were treated with the isolated exosomes, and the effects on apoptosis-related proteins HSP27, HSP70, HSP90, and P53 were assessed. All exosomes, Cur-Exo, TMZ-Exo, and TMZ+Cur-Exo increased cleaved caspase 3, Bax, and P53 proteins, while reducing HSP27, HSP70, HSP90, and Bcl2 proteins. Moreover all treatment groups increased apoptosis in naïve U87 recipient cells. Exosomes released from treated U87 cells had less BDNF and more TNF-α compared to exosomes released from naive U87 cells. In conclusion, we showed for the first time that exosomes released from drug-treated U87 cells could be a new therapeutic approach in glioblastoma, and could reduce the side effects produced by drugs alone. This concept needs to be further examined in animal models before clinical trials could be considered.
AB - Glioblastoma (GBM) remains the most lethal brain tumor without any curative treatment. Exosomes can mediate cell-to-cell communication, and may function as a new type of targeted therapy. In this study, the therapeutic benefits of exosomes generated by U87 cells treated with curcumin and/or temozolomide were investigated. The cells were cultured and treated with temozolomide (TMZ), curcumin (Cur), or their combination (TMZ+Cur). Exosomes were isolated with a centrifugation kit and characterized using DLS, SEM, TEM, and Western blotting. The levels of exosomal BDNF and TNF-α were measured. Naïve U87 cells were treated with the isolated exosomes, and the effects on apoptosis-related proteins HSP27, HSP70, HSP90, and P53 were assessed. All exosomes, Cur-Exo, TMZ-Exo, and TMZ+Cur-Exo increased cleaved caspase 3, Bax, and P53 proteins, while reducing HSP27, HSP70, HSP90, and Bcl2 proteins. Moreover all treatment groups increased apoptosis in naïve U87 recipient cells. Exosomes released from treated U87 cells had less BDNF and more TNF-α compared to exosomes released from naive U87 cells. In conclusion, we showed for the first time that exosomes released from drug-treated U87 cells could be a new therapeutic approach in glioblastoma, and could reduce the side effects produced by drugs alone. This concept needs to be further examined in animal models before clinical trials could be considered.
KW - Cell-cell communication
KW - Curcumin
KW - Exosomes
KW - Glioblastoma
KW - Temozolomide
UR - http://www.scopus.com/inward/record.url?scp=85151879223&partnerID=8YFLogxK
U2 - 10.1016/j.prp.2023.154427
DO - 10.1016/j.prp.2023.154427
M3 - Article
C2 - 37028110
AN - SCOPUS:85151879223
SN - 0344-0338
VL - 245
JO - Pathology Research and Practice
JF - Pathology Research and Practice
M1 - 154427
ER -
