Hernandonine-mediated autophagic cell death in hepatocellular carcinoma: Interplay of p53 and YAP signaling pathways.
Free Radic Biol Med
; 222: 456-466, 2024 Sep.
Article
em En
| MEDLINE
| ID: mdl-38950659
ABSTRACT
Hepatocellular carcinoma (HCC), the primary form of liver cancer, is the third leading cause of cancer-related death globally. Hernandonine is a natural alkaloid derived from Hernandia nymphaeifolia that has been shown to exert various biological functions. In a previous study, hernandonine was shown to suppress the proliferation of several solid tumor cell lines without affecting normal human cell lines. However, little is known about the effect of hernandonine on HCC. Therefore, this study aimed to investigate the effect and mechanism of hernandonine on HCC in relation to autophagy. We found that hernandonine inhibited HCC cell growth in vitro and in vivo. In addition, hernandonine elicited autophagic cell death and DNA damage in HCC cells. RNA-seq analysis revealed that hernandonine upregulated p53 and Hippo signaling pathway-related genes in HCC cells. Small RNA interference of p53 resulted in hernandonine-induced autophagic cell death attenuation. However, inhibition of YAP sensitized HCC cells to hernandonine by increasing the autophagy induction. This is the first study to illustrate the complex involvement of p53 and YAP in the hernandonine-induced autophagic cell death in human HCC cells. Our findings provide novel evidence for the potential of hernandonine as a therapeutic agent for HCC treatment.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
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Proteína Supressora de Tumor p53
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Carcinoma Hepatocelular
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Proliferação de Células
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Morte Celular Autofágica
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Proteínas de Sinalização YAP
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Neoplasias Hepáticas
Limite:
Animals
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Humans
Idioma:
En
Revista:
Free Radic Biol Med
/
Free radic. biol. med
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Free radical biology and medicine
Assunto da revista:
BIOQUIMICA
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MEDICINA
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Taiwan
País de publicação:
Estados Unidos