Cytotoxic effects of Juniperus procera leaf and fruit extracts on human liver cancer cells: In vitro and in silico evaluation

Although there is an increasing body of research focused on natural products for cancer treatment, the therapeutic capabilities of Juniperus procera especially in terms of a comparative analysis of its leaf and fruit extracts against liver cancer have not been thoroughly investigated. This study offers the first detailed examination that integrates both in vitro cytotoxicity assessments and in silico molecular modelling to uncover bioactive compounds from J. procera with targeted anticancer effects on human liver cancer cells (HepG2). The ethanolic extract from the leaves exhibited significant cytotoxicity (IC50 = 17.3 µg/mL), outperforming the fruit extract (IC50 = 24.4 µg/mL), while showing low toxicity to normal human fibroblasts (SI > 2). Molecular docking studies targeting mTOR (PDB: 4JT6) revealed Perylene and Podocarpusflavone A as promising high-affinity ligands (ΔG = -10.9 kcal/mol). Quantitative Structure-Activity Relationship (QSAR) modelling, supported by robust statistical validation (Q² = 0.649, R² = 0.831), indicated that Rutin is likely to exhibit the strongest inhibitory effect (IC50 = 0.011 nM). Additionally, cytotoxicity predictions using the CLC-Pred tool indicated a broad-spectrum efficacy of selected compounds across various liver cancer cell lines, particularly HepG2. This comprehensive approach underscores the potential of new lead compounds derived from J. procera and strongly supports the need for future in vivo and target-specific investigations in liver cancer treatment.