Exploring the anticancer potential of Albizia lebbeck: an integrated computational and in vitro study targeting oral cancer

Oral squamous cell carcinoma (OSCC) poses a significant global health issue, highlighting the need for new treatment options. This study assessed the anticancer effects of phytochemicals from Albizia lebbeck against oral cancer using a combination of in silico and in vitro methods. Network pharmacology revealed important targets related to oral cancer, and compounds such as alpha-gurjunene, β-sitosterol, indene, kaempferol, and quercetin-3- d -xyloside underwent evaluation through drug-likeness predictions, molecular docking, and 200 ns molecular dynamics simulations. The aqueous leaf extract of A. lebbeck was also tested for its antioxidant properties and cytotoxicity against KB cells using DPPH and MTT assays, using doxorubicin as the positive control. Anticancer mechanisms were explored through apoptosis assays, evaluation of reactive oxygen species (ROS) production, wound-healing tests, cell cycle analysis, ELISA, and qRT-PCR. Molecular docking showed that the selected phytochemicals had strong binding affinities for the target proteins. Quercetin-3- d -xyloside achieved the highest XP docking score against AKT1 (− 9.179 kcal/mol), while kaempferol showed the greatest binding affinity against SRC (− 10.519 kcal/mol). Molecular dynamics simulations affirmed stable interactions between the protein and ligands, with hexadecanal (1.86 Å) and α-gurjunene (1.82 Å) showing stability similar to that of the AKT1 reference inhibitor AZD5363 (1.88 Å). Hexadecanal (3.27 Å) and quercetin (3.40 Å) displayed greater backbone stability than the SRC reference inhibitor ponatinib (4.90 Å). The extract demonstrated strong antioxidant activity and dose-dependent cytotoxicity (IC₅₀ = 410.2 µg/mL). It induced apoptosis, inhibited cell movement, affected inflammatory mediators, and adjusted the expression of genes linked to oncogenic signaling, cell growth, apoptosis, and necroptosis. These results indicate that A. lebbeck phytochemicals interact with several targets associated with oral cancer and exhibit promising antioxidant and anticancer properties, warranting further research into their mechanisms and in vivo validation.