Bergenin Triggers Apoptosis in Human Oral Squamous Cell Carcinoma KB Cells by Targeting the PI3K/Akt Pathway: A Biochemical and Molecular Study

Background Bergenin’s anticancer potential in oral squamous cell carcinoma (KB cells) remains underexplored, particularly its modulation of the PI3K/Akt/Nrf2/HO-1 signaling axis. Purpose This study investigates its multimodal effects on apoptosis induction, oxidative stress regulation, and inflammatory-angiogenic pathway suppression. Materials and Methods KB cells were treated with bergenin (100 and 200 µg/mL) and doxorubicin (DOX). Apoptosis was assessed via molecular markers p53, proliferation via Ki-67 staining and oxidative stress via redox assays through ELISA. Pathway components (PI3K/Akt/Nrf2/HO-1) were analyzed using qRT-PCR and Western blot. Statistical significance was evaluated via one-way ANOVA by using GraphPad Prism. PI3K/Akt pathway inhibition was observed alongside Nrf2/HO-1 downregulation ( p < 0.05). Results Oxidative stress mitigation was evidenced by reduced lipid peroxidation and elevated antioxidant enzyme activity ( p < .05). Inflammatory-angiogenic suppression included TNF-α, IL-6, VEGF, and NF-κB reduction ( p < 0.05). Ki-67 expression decreased significantly ( p < .05), and pathway interdependencies were confirmed ( p < .05). Bergenin demonstrated superior NF-κB inhibition compared to DOX ( p < .05). Conclusion Bergenin suppresses KB cell growth primarily through apoptosis and necrosis, mediated by PI3K/Akt pathway inhibition. Its multimodal action—restoring redox balance, disrupting inflammatory-angiogenic networks, and impairing cellular adhesion—highlights its therapeutic potential. Further structural analysis of active components is warranted to validate these findings.