p‐Cymene Targets Multiple Oncogenic Pathways in Hepatocellular Carcinoma: Insights From Network Pharmacology and In Vitro Studies

作者：Nadia Anwar, Muhammad Nasir Hayat Malik, Muhammad Atif, Abdullah R. Alanzi, Hattan A. Alharbi, Waqas Younis, Munawar Abbas, Gideon F. B. Solre · 发表于：Food Science & Nutrition · 年份：2025 · DOI：10.1002/fsn3.71108 · 被引用次数：2 · 研究领域：Genomics, phytochemicals, and oxidative stress、Cancer Mechanisms and Therapy、Ferroptosis and cancer prognosis

This study explored the anticancer potential of p-cymene against hepatocellular carcinoma (HCC) through computational and in vitro approaches. Bioinformatics analysis identified 635 potential targets of p-cymene, with 216 overlapping HCC-related proteins. Target interaction networks were constructed using STRING and Cytoscape, revealing key proteins involved in apoptosis, angiogenesis, and tumor progression. Molecular docking was performed using the molecular operating environment software, demonstrating strong binding affinities of p-cymene with key overlapping HCC targets, including hypoxia-inducible factor 1-alpha (HIF1A), B-cell lymphoma 2 (BCL2), cyclin-dependent kinase 9 (CDK9), Janus kinase 2 (JAK2), vascular endothelial growth factor (VEGF), mitogen-activated protein kinase 4 (MAPK4), tumor protein p53 (P53), signal transducer and activator of transcription 3 (STAT3), and caspase-3 (CASP3). HepG2 cells were treated with increasing concentrations of p-cymene (5-50 mM), and cytotoxicity was assessed using MTT, crystal violet, and trypan blue exclusion assays. Antioxidant activity was measured by evaluating superoxide dismutase (SOD) and glutathione (GSH) levels. Apoptotic markers, including CASP3, P53, VEGF, and BCL2, were quantified using ELISA. Results showed a dose-dependent reduction in HepG2 cell viability, with significant cytotoxic effects at higher p-cymene concentrations (30 and 50 mM). p-Cymene reduced oxidative stress, evident from increased SOD and GSH level...