Melatonin potentiates cisplatin-induced apoptosis and cell cycle arrest in human lung adenocarcinoma cells

These data demonstrate that melatonin enhanced cisplatin-induced cytotoxicity and apoptosis in SK-LU-1 lung cancer cells. SK-LU-1 cell population growth inhibition was mediated by cell cycle arrest in the S phase. These findings suggest that melatonin has the potential to be used for NSCLC treatment in combination with a chemotherapeutic agent such as cisplatin.

Cells of the SK-LU-1 line were treated with melatonin alone at 1-5 mM concentration or cisplatin alone 10-200 μM, for 48 h in culture. Cytotoxicity was measured by MTT reduction assay. Apoptosis induction was detected by annexin V/PI staining using flow cytometric analysis and DAPI nuclear staining. Change in mitochondrial membrane potential (ΔΨm) was quantified using DiOC6(3) reagent and activities of caspases-3/7 were also investigated. DNA fractions were measured using propidium iodide (PI) staining.

Melatonin or cisplatin alone had 50% (IC50 ) cytotoxicity at 5 mM or 34 μM concentrations respectively. Combination of 1 or 2 mM melatonin and cisplatin significantly augmented cytotoxicity of cisplatin by reducing its IC50 to 11 and 4 μM, respectively. Consistently, combined treatment increased population of apoptotic cells by elevating mitochondrial membrane depolarization, activating caspases-3/7 and inducing cell cycle arrest in the S phase, compared to treatment with cisplatin alone.