Synergistic Induction of Apoptosis by Boswellic Acid and Cisplatin in A549 Lung Cancer Cells Through NF-κB Modulation and p53 Pathway Activation.

Abstract

The increasing resistance to chemotherapeutic agents in lung cancer significantly contributes to its high mortality. Natural compounds such as acetyl-11-keto-β-boswellic acid (AKBA) have emerged as promising adjuncts to standard therapies. This study investigated the synergistic apoptotic and cytotoxic effects of AKBA in combination with cisplatin (Cis) on A549 non-small-cell lung cancer (NSCLC) cells. Cell viability, apoptosis, and gene expression were evaluated using MTS assay, Annexin V-FITC/PI staining, caspase activity, RT-qPCR, and ELISA, complemented by molecular docking (AKBA-p53) and molecular dynamics (AKBA-p53 and Cis-p53) analyses. Combined AKBA + Cis treatment significantly enhanced apoptosis and reduced cell viability compared to monotherapies (p < 0.001), accompanied by upregulation of p53 and caspase-3 and suppression of NF-κB. In silico results further supported direct and stable binding of p53, particularly with AKBA. These findings indicate that AKBA synergizes with Cis to potentiate apoptotic and anti-inflammatory responses in NSCLC and may provide a novel dose-sparing strategy with improved therapeutic efficacy, warranting further in vivo validation.