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

Bozkurt A. S.

Journal of research in veterinary medicine (Online), vol.44, no.1, pp.35-41, 2025 (TRDizin)

Abstract

The emergence of drug resistance and limited efficacy of conventional chemotherapeutics have prompted the search for alternative antican- cer strategies. This study aimed to investigate the antiproliferative effects of Capsaicin (CAP) and Leflunomide (LEF), alone and in combi- nation, in murine Lewis lung carcinoma (LLC-1) cells. Following IC₅₀ determination via the Sulforhodamine B (SRB) assay, combination experiments were conducted using sub-IC₅₀ concentrations, and synergistic interactions were assessed through SynergyFinder software and CellTiter-Glo validation. Capsaicin and Leflunomide exhibited dose-dependent cytotoxicity, with IC₅₀ values of 177.68 μM and 41.53 μM, respectively. Although limited cytotoxicity was observed with monotherapies at low doses, their combination produced a statistically sig- nificant synergistic effect (Combination Index = 0.13), resulting in enhanced growth inhibition and reduced colony formation capacity. Mechanistically, the combination is proposed to induce cancer cell death through dual targeting of intracellular calcium/oxidative stress (via TRPV1 activation by Capsaicin) and pyrimidine biosynthesis (via DHODH inhibition by Leflunomide). These findings highlight a promising multi-targeted strategy that suppresses cancer cell proliferation while potentially minimizing systemic toxicity. The Capsaicin–Leflunomide combination may offer a novel therapeutic approach in the treatment of aggressive and drug-resistant lung tumors, warranting further inves- tigation in preclinical models.