| Autor: |
Xuxiu Lu, Fengli Yuan, Liang Qiao, Yankai Liu, Qianqun Gu, Xin Qi, Jing Li, Dehai Li, Ming Liu |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
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| Zdroj: |
Biomedicine & Pharmacotherapy, Vol 171, Iss , Pp 116099- (2024) |
| Druh dokumentu: |
article |
| ISSN: |
0753-3322 |
| DOI: |
10.1016/j.biopha.2023.116099 |
| Popis: |
Chronic myelogenous leukemia (CML) is characterized by the constitutive activation of BCR-ABL tyrosine kinase. Imatinib was approved for CML therapy, however, BCR-ABL-dependent drug resistance, especially BCR-ABL-T315I mutation, restricts its clinical application. In this study, we reported anthraquinone lactone AS1041, a synthesized derivative of marine natural compound Aspergiolide A, showed anti-leukemia effect in vitro and in vivo by promoting cell senescence. Mechanistic study revealed the pro-senescence effect of AS1041 was dependent on oxidative stress-induced DNA damage, and the resultant activation of P53/P21 and P16INK4a/Rb. Also, AS1041 promoted ubiquitin proteasome system (UPS)-mediated BCR-ABL degradation, which also contributed to AS1041-induced senescence. In vivo, AS1041-induced senescence promoted tumor growth inhibition. In summary, the in vitro and in vivo antitumor effect of AS1041 suggests it can serve as a pro-senescence agent for alternative antileukemia therapy and imatinib-resistant cancer therapy by enhancing cellular oxidative stress and BCR-ABL degradation. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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