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Tytuł pozycji:

Novel Small Molecular Compound AE-848 Potently Induces Human Multiple Myeloma Cell Apoptosis by Modulating the NF-κB and PI3K/Akt/mTOR Signaling Pathways

Tytuł:
Novel Small Molecular Compound AE-848 Potently Induces Human Multiple Myeloma Cell Apoptosis by Modulating the NF-κB and PI3K/Akt/mTOR Signaling Pathways
Autorzy:
Xu Y
Feng X
Zhou Q
Jiang W
Dai Y
Jiang Y
Liu X
Li S
Wang Y
Wang F
Li A
Zheng C
Temat:
small molecular compound
ae-848
multiple myeloma
apoptosis
nf-κb and pi3k/akt/mtor pathway
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
RC254-282
Źródło:
OncoTargets and Therapy, Vol Volume 13, Pp 13063-13075 (2020)
Wydawca:
Dove Medical Press, 2020.
Rok publikacji:
2020
Kolekcja:
LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Typ dokumentu:
article
Opis pliku:
electronic resource
Język:
English
ISSN:
1178-6930
Relacje:
https://www.dovepress.com/novel-small-molecular-compound-ae-848-potently-induces-human-multiple--peer-reviewed-article-OTT; https://doaj.org/toc/1178-6930
Dostęp URL:
https://doaj.org/article/306c99ac374e4fa6a3323d92dfd58bde  Link otwiera się w nowym oknie
Numer akcesji:
edsdoj.306c99ac374e4fa6a3323d92dfd58bde
Czasopismo naukowe
Yaqi Xu,1– 3 Xiaoli Feng,4 Qian Zhou,1,2,5 Wen Jiang,1,2,6 Yibo Dai,1– 3 Yang Jiang,1– 3 Xiaoli Liu,1– 3 Shuo Li,1,2,7 Yongjing Wang,1– 3 Fang Wang,6 Ai Li,1– 3 Chengyun Zheng1– 3 1Department of Hematology, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, People’s Republic of China; 2Institute of Biotherapy for Hematological Malignancies, Shandong University, Jinan, Shandong, People’s Republic of China; 3Shandong University-Karolinska Institute Collaboration Laboratory for Stem Cell Research, Jinan, Shandong, People’s Republic of China; 4Clinical Laboratory, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, People’s Republic of China; 5Department of Hematology, Linyi Central Hospital, Linyi, Shandong, People’s Republic of China; 6Institute of Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, People’s Republic of China; 7Binzhou Medical University Hospital, Binzhou, Shandong, People’s Republic of ChinaCorrespondence: Chengyun Zheng; Ai LiHematology Department of the Second Hospital of Shandong University, 247th of Beiyuan Road, Jinan, Shandong, People’s Republic of ChinaTel +86 13675319282; +86 176 6008 0688Email zhengchengyun186@126.com; aili1976@126.comBackground: We aimed to investigate the anti-multiple myeloma (MM) activity of the new small molecular compound AE-848 (5-bromo-2-hydroxyisophthalaldehyde bis[(1-methyl-1H-benzimidazol-2-yl)hydrazone]) and its underlying anti-MM mechanism.Methods: Cell viability and apoptosis were detected and quantified by using MTT and flow cytometry, respectively. JC-1 dye-related techniques were used to assess mitochondrial membrane potential (MMP). Western blotting was applied to detect the expression of NF-κB and PI3K/Akt/mTOR pathway-associated proteins. The in vivo activity of AE-848 against MM was evaluated in a MM mouse model.Results: Application of AE-848 into the in vitro cell culture system significantly reduced the viability and induced apoptosis of the MM cell lines, RPMI-8226 and U266, in a dose- and time-dependent manner, respectively. JC-1 dye and Western blotting analysis revealed that AE-848 induced the cleavage of caspase-8, caspase-3, and poly ADP-ribose polymerase (PARP), resulting in loss of mitochondrial membrane potential (MMP). Both the NF-κB and PI3K/AKT/mTOR signaling pathways were involved in AE-848-induced apoptosis of U266 and RPMI8226 cells. Moreover, AE-848 leads to cell cycle arrest of MM cells. Its anti-MM efficacy was further confirmed in a xenograft model of MM. AE-848 administration significantly inhibited MM tumor progression and prolonged the survival of MM-bearing mice. More importantly, our results demonstrated that AE-848 markedly induced primary MM cell apoptosis.Conclusion: Our results for the first time showed that the small compound AE-848 had potent in vitro and in vivo anti-myeloma activity, indicating that AE-848 may have great potential to be developed as a drug for MM treatment.Keywords: small molecular compound, AE-848, multiple myeloma, apoptosis, NF-κB and PI3K/Akt/mTOR pathway
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