Dendrobium nobile active ingredient Dendrobin A against hepatocellular carcinoma via inhibiting nuclear factor kappa-B signaling

Dendrobin A, a typical active ingredient of the traditional Chinese medicine Dendrobium nobile , has potential clinical application in cancer treatment; however, its effect and mechanism in anti-hepatocellular carcinoma (HCC) remain unsolved. The effects of Dendrobin A on the viability, migration, invasion, cycle, apoptosis, and epithelial-mesenchymal transition of HepG2 and SK-HEP-1 cells were verified by in vitro experiments. mRNA sequencing was performed to screen the differentially expressed genes (DEGs) of HCC cells before and after Dendrobin A treatment, following GO enrichment and KEGG signaling pathway analyses. Mechanistically, molecular docking was used to evaluate the binding of Dendrobin A with proteins p65 and p50, before further verifying the activation of nuclear factor kappa-B (NF-κB) signaling. Finally, the antiproliferative effect of Dendrobin A on HCC cells was explored through animal experiments. Dendrobin A arrested cell cycle, induced apoptosis, and inhibited proliferation, migration, invasion, and blocked epithelial-mesenchymal transition in HepG2 and SK-HEP-1 cells. mRNA sequencing identified 830 DEGs, involving various biological processes. KEGG analysis highlighted NF-κB signaling. Molecular docking revealed strong binding of Dendrobin A with p65 and p50 proteins, and western blotting confirmed reduced levels of p-p65 and p-p50 in HCC cells post Dendrobin A treatment. NF-κB agonist PMA reversed Dendrobin A-inhibited cell proliferation migration and invasion. In vivo experiments showed that Dendrobin A inhibited HCC cell growth. Our findings suggest that Dendrobin A exhibits anti-HCC properties by inhibiting the activation of the NF-κB pathway. These results provide a scientific basis for utilizing Dendrobium nobile in anti-HCC therapies. The active compound Dendrobin A, derived from Dendrobium nobile , exhibits significant anti-hepatocellular carcinoma effects. Its anti-cancer mechanism mainly involves inhibiting the NF-κB signaling pathway to suppress tumor cell proliferation, migration, invasion, epithelial-mesenchymal transition, block cell cycle progression, and induce cell apoptosis. • Dendrobine A from Dendrobium nobile shows promise as an anti-HCC agent due to its multiple anti-cancer properties. • Dendrobine A inhibits the proliferation of HCC cells by arresting the cell cycle at the G2-M phase. • Dendrobine A induces apoptosis and inhibits the epithelial-mesenchymal transition of HCC cells. • The anti-HCC effects of Dendrobine A are related to its inhibition of the activation of NF-κB signaling.