Synergistic Antiproliferative Impact of Capsaicin and Leflunomide in Murine Lung Cancer Cells

Cancer remains a major global health issue, with resistance to conventional therapies driving the need for novel treatment strategies. This study investigated the synergistic effects of capsaicin (CAP), a natural bioactive compound, and Leflunomide (LEF), an immunosuppressive drug, in a murine lung cancer cell line. Capsaicin activates TRPV1 receptors, increasing intracellular calcium levels, while Leflunomide inhibits Dihydroorotate Dehydrogenase (DHODH), disrupting pyrimidine biosynthesis. Although neither agent exhibited significant cytotoxicity at low doses when applied individually, their combination resulted in a synergistic induction of cell death. These findings suggest that the combination of capsaicin and Leflunomide effectively limits cancer cell adaptation through metabolic and oxidative stress pathways, offering a promising anticancer mechanism. The results highlight the potential of this combination therapy for aggressive tumors such as lung cancer, emphasizing the need for further preclinical and clinical investigations.