ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Pharmacology of Anti-Cancer Drugs
Targeted Lipidomics Meets Transcriptomics: How Cinobufagin Rewires Fatty Acid, Sphingolipid, and Glycerophospholipid Metabolism to Combat Hepatoma cell growth
Provisionally accepted
- Binzhou Medical University - Yantai Campus, Yantai, China
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Hepatocellular carcinoma (HCC) is a common malignant tumor, is characterized by an early stage that is not easy to diagnose and a high mortality rate in the late stage, which is a serious threat to patients' lives. Abnormalities in lipid metabolism are closely related to the development of HCC. Integrating transcriptomics and metabolomics analyses can help in the study of drug mechanism of action. Cinobufagin, is the main active ingredient for chinese medicine Chansu to exert anti-tumor effects, but the effects of cinobufagin on abnormal lipid metabolism in tumor cells are not clear. In this study, we demonstrate through the results of targeted lipid metabolomics that cinobufagin interferes with fatty acyl class, sphingolipids, glycerophospholipids, glycerides, glycolipids, and steroids. The results of integration of transcriptomics and metabolomics identified that intervention in fatty acid metabolism (including biosynthesis of unsaturated fatty acids, fatty acid biosynthesis, fatty acid degradation, and fatty acid elongation), sphingolipid metabolism (including sphingolipid metabolism, glycosphingolipid biosynthesis-globo and isoglobo series, glycosphingolipid biosynthesis-lacto and neolacto series, glycosphingolipid biosynthesis-ganglio series), and glycerophospholipid metabolism (including glycerophospholipid metabolism, ether lipid metabolism, glycosylphosphatidylinositol (GPI)-anchor biosynthesis) may be partially responsible for the effect of anti-hepatoma cell growth induced by cinobufagin. This study is of great significance for the application of cinobufagin and chansu in clinical HCC treatment and promotes the development of new drugs from traditional Chinese medicine in the field of antitumor.
Keywords: Cinobufagin, fatty acid metabolism, Hepatocellular Carcinoma, integration of transcriptomics and metabolomics, Sphingolipid metabolism, targeted lipid metabolomics
Received: 13 Jul 2025; Accepted: 08 Dec 2025.
Copyright: © 2025 Shao, Yu, Xu, Rong and Yang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Ailin Yang
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