Resveratrol coordinates apoptosis and autophagy in hepatocellular carcinoma cells via p53 acetylation: An integrative network pharmacology and experimental validation study.

IF 1.7 4区生物学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Cytotechnology Pub Date : 2026-06-01 Epub Date: 2026-04-30 DOI:10.1007/s10616-026-00973-1

Hui Zhang, Huidong Zhang, Wei Li, Hong Zhang, Yang Xu, Wen Liu, Liya Bao, Siyu Zhou, Xiaoyu Zhang, Jiao Li

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引用次数: 0

Abstract

Hepatocellular carcinoma (HCC) remains a therapeutic challenge due to late-stage diagnosis and suboptimal response to standard therapies. Resveratrol, a plant-derived polyphenol, suppresses proliferation of HCC cells by inducing apoptosis and autophagy. However, the regulatory mechanism that integrates these two processes is poorly understood. This study aimed to elucidate how resveratrol coordinately regulates apoptosis and autophagy in HCC cells. Using integrated network pharmacology and QIAGEN Ingenuity Pathway Analysis (IPA), TP53 was predicted as the central hub target gene of resveratrol in HCC, where it coordinated both apoptosis and autophagy. Molecular docking and molecular dynamics simulation confirmed direct and stable binding of resveratrol to p53 protein. Functional validation in vitro revealed that resveratrol significantly (P < 0.01) inhibited the viability of p53-wild-type HepG2 cells, accompanied by mRNA upregulation of pro-apoptotic and autophagy-related genes (BAX, CASP9, CASP3, ATG5), with concordant changes at the protein level (upregulated Bax and ATG5 proteins, increased ratios of Bax/Bcl-2, cleaved-Caspase 9/Caspase 9, cleaved-Caspase 3/Caspase 3, and LC3B-II/I, decreased p62 protein). These effects were strictly p53-dependent, as they were absent in p53-null Hep3B cells and significantly (P < 0.05) attenuated upon pharmacological inhibition of p53 in HepG2 cells. Mechanistically, resveratrol activated p53 not by increasing its protein level but by enhancing its acetylation at Lysine 382. This study established p53 acetylation as a critical switch through which resveratrol coordinately induced apoptosis and autophagy. These findings provide a mechanistic framework for anti-HCC effect of resveratrol and underscore the therapeutic relevance of p53 activation pathways in HCC.

Supplementary information: The online version contains supplementary material available at 10.1007/s10616-026-00973-1.

查看原文本刊更多论文

白藜芦醇通过p53乙酰化调节肝癌细胞凋亡和自噬：一项综合网络药理学和实验验证研究。

肝细胞癌（HCC）仍然是一个治疗挑战，由于晚期诊断和对标准治疗的次优反应。白藜芦醇是一种植物源性多酚，通过诱导细胞凋亡和自噬来抑制肝癌细胞的增殖。然而，整合这两个过程的调控机制却知之甚少。本研究旨在阐明白藜芦醇如何协调调节肝癌细胞的凋亡和自噬。利用综合网络药理学和QIAGEN Ingenuity Pathway Analysis (IPA)，预测TP53是白藜芦醇在HCC中的中心枢纽靶基因，它协调细胞凋亡和自噬。分子对接和分子动力学模拟证实白藜芦醇与p53蛋白直接稳定结合。体外功能验证显示，白藜芦醇显著（P BAX、CASP9、CASP3、ATG5），蛋白水平变化一致（BAX和ATG5蛋白上调，BAX /Bcl-2、切割-Caspase 9/Caspase 9、切割-Caspase 3/Caspase 3和LC3B-II/I比值升高，p62蛋白降低）。这些效应严格依赖于p53，因为它们在p53缺失的Hep3B细胞中不存在，并且显著(P)补充信息：在线版本包含补充材料，可在10.1007/s10616-026-00973-1获得。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cytotechnology 生物-生物工程与应用微生物

CiteScore

4.10

自引率

0.00%

发文量

审稿时长

6-12 weeks

期刊介绍： The scope of the Journal includes: 1. The derivation, genetic modification and characterization of cell lines, genetic and phenotypic regulation, control of cellular metabolism, cell physiology and biochemistry related to cell function, performance and expression of cell products. 2. Cell culture techniques, substrates, environmental requirements and optimization, cloning, hybridization and molecular biology, including genomic and proteomic tools. 3. Cell culture systems, processes, reactors, scale-up, and industrial production. Descriptions of the design or construction of equipment, media or quality control procedures, that are ancillary to cellular research. 4. The application of animal/human cells in research in the field of stem cell research including maintenance of stemness, differentiation, genetics, and senescence, cancer research, research in immunology, as well as applications in tissue engineering and gene therapy. 5. The use of cell cultures as a substrate for bioassays, biomedical applications and in particular as a replacement for animal models.