Basic Study
Copyright ©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Mar 15, 2025; 17(3): 101174
Published online Mar 15, 2025. doi: 10.4251/wjgo.v17.i3.101174
Tetrahydrocurcumin-induced apoptosis of hepatocellular carcinoma cells involves the TP53 signaling pathway, as determined by network pharmacology
Zhuo-Cong Bao, Ye Zhang, Zhao-Dong Liu, Hui-Jun Dai, Fu Ren, Ning Li, Shang-Yu Lv, Yan Zhang
Zhuo-Cong Bao, Ye Zhang, Zhao-Dong Liu, Graduate School, Shenyang Medical College, Shenyang 110034, Liaoning Province, China
Hui-Jun Dai, Guangxi Medical University Cancer Hospital, Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
Fu Ren, Ning Li, Yan Zhang, Key Laboratory of Human Ethnic Specificity and Phenomics of Critical Illness in Liaoning Province, Shenyang Medical College, Shenyang 110034, Liaoning Province, China
Fu Ren, Ning Li, Yan Zhang, Key Laboratory of Phenomics in Shenyang, Shenyang Medical College, Shenyang 110034, Liaoning Province, China
Ning Li, Yan Zhang, Department of Biochemistry, School of Basic Medicine, Shenyang Medical College, Shenyang 110034, Liaoning Province, China
Shang-Yu Lv, Department of Clinical Medicine, Shenyang Medical College, Shenyang 110034, Liaoning Province, China
Yan Zhang, International Education School, International Exchange and Cooperation Office, Shenyang Medical College, Shenyang 110034, Liaoning Province, China
Co-first authors: Zhuo-Cong Bao and Ye Zhang.
Author contributions: Bao ZC, Zhang Y and Liu ZD performed most of the bench work, analyzed the data, and wrote the manuscript; Dai HJ was responsible for experimental guidance; Ren F provided technical consultation; Li N contributed new reagents and analytic tools; Lv SY collected relevant references and revised the manuscript; Zhang Y designed the experiments; All authors read and approved the final manuscript.
Supported by The Central Government Guides Local Science and Technology Development Fund, No. 2023JH6/100100021; Liaoning Province Education Department Foundation of China, No. JYTMS20231393 and No. LJ212410164032; Scientific Research Project of the Liaoning Province Education Department, No. SYYX2019015; Science and Technology Foundation of Shenyang Medical College, No. 20171004; and the Science and Technology Innovation Fund for Master Students of Shenyang Medical College, No. Y20220509.
Institutional review board statement: The biological samples used in this study are from Wuhan Servicebio Technology Co., Ltd., Wuhan Pricella Biotechnology Co., Ltd. This study is in line with Article 32 of the Measures for the Ethical Review of Life Science and Medical Research Involving Humans, which can be exempted from the scope of ethical review.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: Technical appendix, statistical code, and dataset available from the corresponding author at zhangyan@symc.edu.cn.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Yan Zhang, PhD, Associate Professor, International Education School, International Exchange and Cooperation Office, Shenyang Medical College, No. 146 North Huanghe Street, Shenyang 110034, Liaoning Province, China. zhangyan@symc.edu.cn
Received: September 6, 2024
Revised: December 4, 2024
Accepted: January 16, 2025
Published online: March 15, 2025
Processing time: 161 Days and 2.7 Hours
Abstract
BACKGROUND

Hepatocellular carcinoma (HCC) is a malignant disease with high incidence and mortality worldwide. This study focuses on the TP53 target protein to investigate the potential therapeutic effect of tetrahydrocurcumin (THC) on HCC and its mechanism of action. The research hypothesis is that THC can inhibit the proliferation, migration, and invasion of HCC cells, and promote their apoptosis by regulating the TP53 target protein.

AIM

To explore the mechanism by which THC inhibits HCC cell proliferation via the TP53 signaling pathway.

METHODS

Potential targets of THC and HCC were identified from multiple databases. The core targets were subjected to analyses using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases, and visualization processing, using the online platform Metascape to identify the key molecules and signaling pathways involved in the action of THC against HCC. The molecular mechanisms of action of THC against TP53 in the inhibition of HCC cells were verified using cell counting kit-8, Transwell, apoptosis, and western blotting assays.

RESULTS

Molecular docking results showed that THC had a high score for the TP53 target protein. In vitro experiments indicated that THC effectively inhibited the proliferation and migration of HCC cells, and affected the expression levels of TP53, MDM2, cyclin B, Bax, Bcl-2, caspase-9, and caspase-3.

CONCLUSION

THC induces the apoptosis of HCC cells through the TP53 signaling pathway, thereby inhibiting their proliferation and migration.

Keywords: Hepatocellular carcinoma cells; Tetrahydrocurcumin; TP53; Network pharmacology; Molecular docking

Core Tip: This study investigated the molecular mechanisms by which tetrahydrocurcumin (THC), a derivative of curcumin, inhibits hepatocellular carcinoma cells. Utilizing a comprehensive approach that integrated network pharmacology, molecular docking, and in vitro experiments, the TP53 signaling pathway was identified as a critical mediator of the antitumor activity of THC.