AS1041, a novel derivative of marine natural compound Aspergiolide A, induces senescence of leukemia cells via oxidative stress-induced DNA damage and BCR-ABL degradation

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.PMID:38171244 | DOI:10.1016/j.biopha.2023.116099
Source: Biomedicine and pharmacotherapy = Biomedecine and pharmacotherapie - Category: Drugs & Pharmacology Authors: Source Type: research