Potential Synergistic Interaction Between Curcumin and Sorafenib Enhances Cytotoxicity in NCI-H5222 Lung Cancer Cells

Non-small cell lung cancer (NSCLC), accounting for approximately 85% of lung cancer cases, remains a leading cause of cancer-related mortality. Genetic alteration such as EGFR mutations, tobacco exposure, and resistance to apoptosis, slows its progression and limits therapeutic success. Although targeted therapies and immunotherapy have improved outcomes for select patients, resistance remains a major challenge, highlighting the need for more effective treatments. This study investigated the potential synergistic interaction between curcumin (CUR) and sorafenib (SF) in the p53-null NCI-H522 NSCLC cell line. Cell viability (MTT assay), apoptosis (Hoechst 33342, Rhodamine 123, and Nuclear-ID red/green staining) and protein expression (Western blot) were evaluated following CUR, SF, or combined treatment. The combination markedly increased apoptosis via activation of caspases-3, -7, -8, and -9, elevated Bax/Bcl-2 ratio, and increased ROS production, while suppressing MEK1–4, mTOR, Akt, EGFR, ERK/p-ERK, and HER2. Tumor suppressors p21 and PTEN were upregulated, and cell cycle regulators were downregulated. These findings indicate that CUR potentiates the anticancer effects of SF through multi-pathway inhibition and tumor suppressor activation, supporting its potential as an adjunct therapy for NSCLC, offering a promising strategy to improve NSCLC treatment outcomes.