Selective cytotoxicity of Dendrocnide meyeniana extract and gold nanoparticle-enhanced cytotoxicity in selected human cancer cell lines with gene expression modulation

Dendrocnide meyeniana is a phytochemically diverse plant with previously predicted anticancer potential, although experimental validation remains limited. This study evaluated the cytotoxic and molecular effects of D. meyeniana extract (DE) and its biologically synthesized gold nanoparticle formulation (DE-AuNPs) in human cancer cell lines. Plant identity was confirmed using matK , rbcL , and ITS DNA barcodes, while DE-AuNPs were characterized using UV–Vis spectroscopy, FTIR, SEM, and EDS. Cytotoxicity was evaluated in COLO201 colorectal adenocarcinoma, HCC1806 breast cancer, and A549 lung cancer cells, with HFL1 fibroblasts used as a normal cell model. Both DE and DE-AuNPs exhibited cytotoxic activity against all cancer cell lines, with IC₅₀ values below 30 µg/mL. COLO201 showed the greatest sensitivity, with IC₅₀ values of 11.70 ± 1.85 µg/mL for DE and 12.59 ± 1.91 µg/mL for DE-AuNPs. In contrast, HFL1 fibroblasts exhibited higher IC₅₀ values of 48.31 ± 2.92 and 47.02 ± 2.89 µg/mL, respectively. Selectivity index analysis demonstrated preferential cytotoxicity toward cancer cells, with the highest selectivity observed in COLO201. The effect of nanoparticle formulation varied among cancer cell lines, indicating a cell-line-dependent response. Gene expression analysis revealed differential modulation of genes associated with apoptosis, cell-cycle regulation, proliferation, and metastasis, including prominent p53 upregulation and reduced EGFR expression in selected treatment groups. MMP-9 expression also showed cell-line-dependent modulation. These findings provide experimental evidence that complements previous in silico predictions and support the anticancer potential of D. meyeniana -derived preparations for further mechanistic and translational investigation.