Annonaceous Acetogenins Synergistically Inhibit Hepatocellular Carcinoma with Sorafenib.
J Nat Prod
; 87(1): 14-27, 2024 01 26.
Article
em En
| MEDLINE
| ID: mdl-38233978
ABSTRACT
Sorafenib was first approved as the standard treatment for advanced hepatocellular carcinoma (HCC). Despite providing an advantage in terms of patient survival, sorafenib has shown poor clinical efficacy and severe side effects after long-term treatment. Thus, combination treatment is a potential way to increase the effectiveness and reduce the dose-limiting toxicity of sorafenib. Extracts of the seeds of Annona montana have shown synergistic antitumor activity with sorafenib, and seven annonaceous acetogenins, including three new acetogenins, muricin P (2), muricin Q (3), and muricin R (4), were isolated from the extracts by bioguided fractionation and showed synergy with sorafenib. The structures of these compounds were determined using spectroscopic and chemical methods. Annonacin (1) and muricin P (2), which reduced intracellular ATP levels and promoted apoptosis, exhibited synergistic cytotoxicity with sorafenib in vitro. In vivo, annonacin (1) displayed synergistic antitumor activity by promoting tumor cell apoptosis. Moreover, the potential mechanism of annonacin (1) was predicted by transcriptomic analysis, which suggested that SLC33A1 is a potential target in HCC. Annonacin (1) might be a novel candidate for combination therapy with sorafenib against advanced HCC.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Carcinoma Hepatocelular
/
Furanos
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Lactonas
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Neoplasias Hepáticas
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Antineoplásicos Fitogênicos
Limite:
Humans
Idioma:
En
Revista:
J Nat Prod
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China