Potential of the combination of Artemisia absinthium extract and cisplatin in inducing apoptosis cascades through the expression of p53, BAX caspase 3 ratio, and caspase 9 in lung cancer cells (Calu-6)

Introduction: Artemisia has received attention in treating cancer because of having bioactive components, antiproliferative and anti-inflammatory properties. The present study assessed the synergistic effect of Artemisia absinthium extract and cisplatin on Calu-6 human lung cancer cells.Methods: Separation and identification of extract components were assessed by TLC, HPLC-MS, and GC-MS. The cell viability, and antiproliferative activity of A. absinthium extract and cisplatin was measured separately and synergistically by MTT. Additionally, nuclear morphological changes were evaluated through DAPI staining. Annexin V/PI test and real-time PCR technique were respectively applied to determine apoptosis induction, and variations in expression level of P53, caspas-3 and 9, and BAX genes.Results: The important components including costunolide, thujone, and artemisinin were identified in Artemisia absinthium extract. Extract, cisplatin, and their combination MTT results showed inhibited proliferation of Calu-6 cells in a dose-dependent manner. This combination significantly reduced the cell viability in comparison to control (p < 0.001). DAPI staining results represented cell nuclear morphological changes including nuclear chromatin condensation, apoptotic body formation, and cell membrane shrinkage. Further, Annexin V/PI test and alterations in expression level of the apoptosis-involved genes revealed an increase in apoptosis in Calu-6 cells.Conclusion: The A. absinthium extract could enhanced cell sensitivity of cisplatin by its active compounds. The treatment with A. absinthium extract + cisplatin may reduce cisplatin side-effects in lung cancer cells through declining the dosage along with utilizing the potential of plant constituents. Finally, Artemisia can be suggested as an adjunctive compound with less side effects for lung cancer therapy.