肝细胞癌（HCC）是肝癌的主要形式，是全球癌症相关死亡的第三大原因。 Hernandonine 是一种从 Hernandia nymphaeifolia 中提取的天然生物碱，已被证明具有多种生物学功能。在之前的一项研究中，赫南酮宁被证明可以抑制几种实体瘤细胞系的增殖，而不影响正常人类细胞系。然而，人们对 Hernandonine 对 HCC 的影响知之甚少。因此，本研究旨在探讨hernandonine对HCC与自噬相关的作用及其机制。我们发现 Hernandonine 在体外和体内抑制 HCC 细胞生长。此外，hernandonine 还可引起 HCC 细胞自噬细胞死亡和 DNA 损伤。 RNA-seq 分析显示 Hernandonine 上调 HCC 细胞中 p53 和 Hippo 信号通路相关基因。 p53 的小 RNA 干扰导致 Hernandonine 诱导的自噬细胞死亡减弱。然而，抑制 YAP 可以通过增加自噬诱导使 HCC 细胞对 Hernandonine 敏感。这是第一项阐明 p53 和 YAP 在赫南酮宁诱导的人类 HCC 细胞自噬细胞死亡中复杂参与的研究。我们的研究结果为 Hernandonine 作为 HCC 治疗药物的潜力提供了新的证据。版权所有 © 2024。由 Elsevier Inc. 出版。

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.Copyright © 2024. Published by Elsevier Inc.