Bruceine A Inhibits Cell Proliferation by Targeting the USP13/PARP1 Signalling Pathway in Multiple Myeloma

Basic & Clinical Pharmacology & Toxicology, Journal Year: 2025, Volume and Issue: 136(5)

Published: March 28, 2025

ABSTRACT Multiple myeloma (MM) is an incurable hematologic malignancy, driving significant interest in the discovery of novel therapeutic strategies. Bruceine A (BA), a tetracyclic triterpene quassinoid derived from Brucea javanica , has shown anticancer properties by modulating multiple intracellular signalling pathways and exhibiting various biological effects. However, specific pharmacological mechanisms which it combats MM remain unclear. In this study, we identified USP13 as potential target BA. We observed increase expression patients with MM, was strongly associated poorer prognosis. Furthermore, enhanced can stimulate cell proliferation both vitro vivo. Mass spectrometry analysis, combined co‐immunoprecipitation ubiquitination experiments, revealed PARP1 critical downstream USP13. stabilize protein through deubiquitination, promoting PARP1‐mediated DNA damage repair (DDR) facilitating progression. Notably, utilized lines, Patient‐Derived Tumour Xenograft model, 5TMM3VT mouse model to determine effects BA on progression, revealing its USP13/PARP1 disrupt DDR cells. conclusion, these findings suggest that inhibiting USP13/PARP1‐mediated might be promising strategy for MM.

Language: Английский

The quassinoids bruceines A–M: pharmacology, mechanism of action, synthetic advance, and pharmacokinetics—a review

Naunyn-Schmiedeberg s Archives of Pharmacology, Journal Year: 2024, Volume and Issue: 397(12), P. 9417 - 9433

Published: July 10, 2024

Language: Английский