Zhang X, Wang LQ, Liu ZY. Senegenin suppresses hepatocellular carcinoma by regulating O-GlcNAcylation. World J Gastrointest Oncol 2024; 16(9): 3994-4005 [DOI: 10.4251/wjgo.v16.i9.3994]
Corresponding Author of This Article
Zhi-Yong Liu, MD, Associate Chief Physician, Department of Traditional Chinese Medicine, Qingpu Branch of Zhongshan Hospital Affiliated to Fudan University, No. 1158 Park Road East, Qingpu District, Shanghai 201700, China. lzhy780404@163.com
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Basic Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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: http://creativecommons.org/licenses/by-nc/4.0/
World J Gastrointest Oncol. Sep 15, 2024; 16(9): 3994-4005 Published online Sep 15, 2024. doi: 10.4251/wjgo.v16.i9.3994
Senegenin suppresses hepatocellular carcinoma by regulating O-GlcNAcylation
Xiang Zhang, Li-Qiong Wang, Zhi-Yong Liu
Xiang Zhang, Zhi-Yong Liu, Department of Traditional Chinese Medicine, Qingpu Branch of Zhongshan Hospital Affiliated to Fudan University, Shanghai 201700, China
Li-Qiong Wang, Department of Hepatology, Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China
Co-first authors: Xiang Zhang and Li-Qiong Wang.
Author contributions: Zhang X and Wang LQ drafted the manuscript, performed the experiments, and prepared the figures; Liu ZY checked and guided for this manuscript; Zhang X and Wang LQ contributed equally to this work.
Institutional animal care and use committee statement: Upon review, it has been determined that this study does not involve interventions or interactions with human or animal subjects, nor does it involve access to identifiable private information. The research scope is confined to the use of established cell lines, which are fully compliant with ethical standards for research without direct involvement of human or animal subjects.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: The data used to support the findings of this study are available from the corresponding author upon request at lzhy780404@163.com.
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: Zhi-Yong Liu, MD, Associate Chief Physician, Department of Traditional Chinese Medicine, Qingpu Branch of Zhongshan Hospital Affiliated to Fudan University, No. 1158 Park Road East, Qingpu District, Shanghai 201700, China. lzhy780404@163.com
Received: May 21, 2024 Revised: July 4, 2024 Accepted: August 1, 2024 Published online: September 15, 2024 Processing time: 110 Days and 13.5 Hours
Abstract
BACKGROUND
Based on current knowledge, hepatocellular carcinoma (HCC) is a condition with numerous etiologies and risk factors. However, the pathogenesis of HCC remains unclear.
AIM
To investigate the roles of senegenin and O-GlcNAcylation in the growth and metastasis of HCC.
METHODS
The levels of O-linked N-acetylglucosamine transferase (OGT) and O-GlcNAcylation in HCC cells and tissues were detected using western blot analysis. The effects of senegenin and O-GlcNAcylation on the proliferation of HCC cells were investigated in vitro using cell counting kit-8 and clonogenic assays. The potential effects of senegenin and O-GlcNAcylation on HCC metastasis were examined using the transwell migration assay. O-GlcNAcylation levels were altered via drug treatment and lentiviral infection, and western blot analysis was used to detect proteins involved in various pathways.
RESULTS
Western blot analysis revealed that OGT and O-GlcNAcylation levels were significantly elevated in HCC tissues and cells. O-GlcNAcylation levels in HCC cells were significantly altered by drug treatment and lentiviral infection. An increase in the glycosylation level was linked to enhanced proliferation, invasiveness, clonogenicity, and metastatic potential of cancer cells. O-GlcNAcylation induced by senegenin was found to slow the proliferation and migration of HCC cells. The levels of proteins involved in nuclear factor-kappa B (NF-κB) and c-Jun N-terminal kinase (JNK) pathways, which are associated with endoplasmic reticulum stress, were altered.
CONCLUSION
Senegenin lowers O-GlcNAcylation levels, decreases OGT expression, and inhibits cancer cell growth and metastasis by regulating proteins involved in NF-κB and JNK pathways.
Core Tip: This study investigated the effects of senegenin and O-GlcNAcylation on the growth and metastasis of hepatocellular carcinoma (HCC) cells. The findings indicated that O-GlcNAcylation levels are elevated in HCC tissues and cells, and senegenin can reduce these levels by targeting proteins involved in nuclear factor-kappa B and c-Jun N-terminal kinase signaling pathways. This modulation decreases the levels of O-linked N-acetylglucosamine transferase and inhibits the proliferation and metastasis of HCC cells, providing new therapeutic targets for liver cancer.
