ArticleBMC complementary medicine and therapies2023
Network pharmacological analysis of corosolic acid reveals P4HA2 inhibits hepatocellular carcinoma progression.
Article in BMC complementary medicine and therapies, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 9 citations in OpenAlex.
- Collagen Prolyl 4-Hydroxylase: An Emerging Key Player in Cardiac Fibrosis.Journal of cardiovascular translational research · 2026Review
- CCDC137 affects sorafenib resistance in hepatocellular carcinoma cells by activating the AKT/mTOR signaling pathway.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Article
- A review of the pharmacological mechanism of corosolic acid.Frontiers in pharmacology · 2026Review
- Targeting collagen Prolyl 4-hydroxylase for cancer treatment.Medical oncology (Northwood, London, England) · 2025Review
- Prolyl 4-hydroxylase subunit alpha-2 acts as a TRIM21 ubiquitination substrate to promote papillary thyroid cancer progression via the glycolytic pathway.Cell death & disease · 2025Article
- The association between sugar-sweetened beverage consumption, muscle strength, and psychological symptoms among Chinese adolescents: a multicenter cross-sectional survey.Frontiers in nutrition · 2025Article
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundCorosolic acid is a pentacyclic triterpene acid with hypoglycemic, anti-inflammatory, and anti-cancer effects. However, its potential targets in hepatocellular carcinoma (HCC) are unknown, hindering clinical utilization.
methodsDifferentially expressed proteins of the Bel-7404 cell line were identified with tandem mass tag analysis and differentially expressed genes (DEGs) of an HCC TCGA dataset using bioinformatics. Gene functions and pathways were inferred using the DAVID database. Online databases were used to establish P4HA2 expression in HCC (GEPIA2) and its relationship with patient survival (UALCAN and The Human Protein Atlas), the association between P4HA2 expression and immune cell infiltration (TIMER2), and DNA methylation of the P4HA2 gene (MethSurv). Cell proliferation, cell cycle, and cell death were assessed with PI and SYTOX-Green staining, CCK-8, and colony formation assays. Protein expression levels were detected by Western blotting.
resultsA total of 44 differentially expressed proteins and 4498 DEGs were identified. Four genes whose proteins were also found in the differential protein profile but with opposing expressions were selected as candidate targets. The candidate gene prolyl 4-hydroxylase subunit alpha 2 (P4HA2) was recognized as the only potential target due to its high expression in public datasets, association with poor patient survival, and relation to immune cell infiltration in HCC tissues. Moreover, the DNA methylation status in 4 CpG islands of the P4HA2 gene correlated with a poor prognosis. Furthermore, corosolic acid treatment inhibited the proliferation of HCC cell lines Bel-7404 and HepG2 in a dose-dependent manner, caused G2/M phase cell cycle arrest, and promoted cell death. In addition, the treatment reduced P4HA2 protein levels.
conclusionOur results indicate that P4HA2 is a potential target of corosolic acid. Thus, they contribute to understanding molecular changes in HCC after corosolic acid treatment and facilitate finding new treatment regimens.
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