<i>Lantana camara</i> L. leaf extract-loaded chitosan nanoparticles induce apoptosis and suppress PI3K/AKT and NF-κB signalling in triple-negative breast (MDA-MB-231) and colorectal cancer (HCT116) cells

Triple-negative breast cancer and colorectal cancer are aggressive malignancies with limited response to standard chemotherapy. Lantana camara L. (Verbenaceae), a medicinal plant rich in bioactive compounds, was investigated for its anticancer potential through leaf extract-loaded chitosan nanoparticles (LC-ChNPs). Methanol extract was encapsulated by ionic gelation, and nanoparticles were characterized for size, charge, and encapsulation efficiency. Cytotoxicity was assessed using the MTT assay, while mechanistic studies involved flow cytometry, DCFDA-based ROS detection, caspase-3 activity assay, qRT-PCR, and Western blotting. GC-MS profiling identified lantadene A (22.7%), caryophyllene oxide (12.4%), and oleanolic acid (7.9%) as major constituents. LC-ChNPs had a mean sizeof 168.4 ± 2.7 nm, zeta potential of +32.1 mV, and 81.3% encapsulation efficiency. Potent cytotoxicity was observed with IC₅₀ values of 18.6 ± 1.2 μg/mL (MDA-MB-231) and 22.4 ± 1.5 μg/mL (HCT116). Treatment increased ROS generation (4.2- and 3.9-fold), enhanced caspase-3 activity (3.8-fold), suppressed Bcl-2 (68%), and upregulated Bax and p53 (3.1- and 2.6-fold). Key oncogenic proteins PI3K, AKT, and NF-κB (p65) were strongly downregulated. LCChNPs also synergized with doxorubicin (CI = 0.61). These findings suggest that LC-ChNPs exert significant in vitro anticancer effects through apoptosis induction and inhibition of PI3K/AKT/NF-κB signalling, highlighting their potential as a novel targeted phytomedicine.