Evaluation of the Cytotoxic Effects of Plantago lanceolata L. Extract and Its Combinations with Chemotherapeutic Agents on Lung Cancer Cells

Abstract

Lung cancer remains the leading cause of cancer-related deaths worldwide, underscoring the urgent need for safe and effective therapeutic strategies. In this context, Plantago lanceolata L., a medicinal plant traditionally used in the treatment of respiratory disorders, has attracted growing scientific interest due to its rich phytochemical composition and potential anticancer properties. This study investigates the cytotoxic effects of a methanolic extract obtained from P. lanceolata L., alone and in combination with conventional chemotherapeutic agents such as Methotrexate and Cytarabine (Alexan), on human lung adenocarcinoma (A549) cells and murine macrophage (J774) cell lines. Previous studies have demonstrated the antiproliferative activity of Plantago species and the dose-dependent cytotoxic effects of their phenylethanoid glycosides (e.g., acteoside, plantamajoside) across various cancer cell lines. In the present study, comparable anticancer efficacy was achieved using substantially lower doses of the plant extract than those previously reported. Furthermore, the extract preserved the viability of immune cells, suggesting potential M1 macrophage activation and an immunomodulatory role. This is the first study to evaluate the synergistic effects of P. lanceolata L. in combination with Methotrexate and Alexan against lung cancer cells, offering preliminary evidence supporting its use as an adjunct phytotherapeutic agent. The findings demonstrate selective toxicity of the extract toward cancer cells with minimal effects on healthy immune cells, highlighting its promising therapeutic potential that warrants further validation through in vivo and mechanistic investigations.