Abstract
Objectives: The anti-cancer potential of melatonin has been examined using a variety of experimental approaches. Melatonin immunomodulatory action was evaluated against the lung cancer cell line SK-LU-1, in co-culture with human peripheral blood mononuclear cells (PBMC). Materials and methods: Melatonin was tested on the cell line only after 24 h incubation (direct effect), and on the co-culture system of SK-LU-1 and PBMC to investigate any indirect effect. Apoptotic induction of the cancer cells was assessed using annexin V/PI staining with flow cytometric analysis for membrane alteration. Intracellular superoxide anion (O2 (•-) ) and hydrogen peroxide (H2 O2 ) for intracellular oxidative stress and glutathione (GSH) for intracellular anti-oxidation were measured with specific fluorescence probes. DNA fractions were measured employing propidium iodide (PI) fluorescence staining. Results: High doses of melatonin were directly toxic to SK-LU-1 cells, while PBMC-mediated indirect effect occurred after moderate doses (1 μm). Under co-culture conditions, increases in apoptotic cell death, increase in oxidative stress by reduction of GSH and cell cycle arrest in G0 /G1 in SK-LU-1 cells, were observed as the immunomodulatory effect of melatonin. Conclusion: Melatonin had indirect effects on lung cancer cells by enhancement of immunomodulatory effects, but further studies of mechanism(s) involved are needed.