EVALUATION OF THE ANTI-ANGIOGENIC EFFECT OF COREOPSIS GRANDIFLORA IN HEPATOCELLULAR CARCINOMA VIA VEGFR2 REGULATION

Abstract

Background: Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality worldwide, with limited therapeutic efficacy and frequent resistance to current targeted agents. VEGFR2-mediated angiogenesis plays a central role in HCC progression, making it a clinically validated therapeutic target. Natural products are increasingly explored as safer, multitarget alternatives to synthetic inhibitors.

Aim: This study aimed to systematically evaluate phytochemicals from Coreopsis grandiflora as potential VEGFR2 inhibitors using an integrative computational pharmacology approach.

Methods: Twenty-five phytochemicals were retrieved from the IMPPAT database and subjected to molecular docking against VEGFR2 (PDB ID: 2OH4). Top-scoring compounds were further screened using Lipinski’s Rule of Five, SwissADME pharmacokinetics, BOILED-Egg gastrointestinal and blood–brain barrier profiling, and PASS biological activity prediction. Target validation was performed through transcriptomic expression analysis and Kaplan–Meier survival assessment. In vitro cytotoxicity of the extract was evaluated in HepG2 cells using the MTT assay.

Results: Docking analysis identified several compounds with strong binding affinity, with the highest score reaching −7.8 kcal/mol. Interaction profiling revealed stable engagement within the ATP-binding pocket of VEGFR2, involving key catalytic residues. Eighteen compounds satisfied drug-likeness criteria, and selected candidates demonstrated favourable pharmacokinetic properties and predicted antineoplastic activity. VEGFR2 was overexpressed in HCC tissues, and higher expression levels were associated with poorer overall survival. Additionally, the extract exhibited dose-dependent cytotoxicity in HepG2 cells with an IC₅₀ of 103.36 µg/mL.

Conclusion: This study identifies Coreopsis grandiflora as a promising botanical source of potential VEGFR2 inhibitors in HCC. By integrating docking, pharmacokinetic screening, biological prediction, and clinical target validation, the findings provide a rational foundation for further experimental investigation into plant-derived anti-angiogenic therapies.