Immunomodulatory effect of melatonin in SK-LU-1 human lung adenocarcinoma cells co-cultured with peripheral blood mononuclear cells

Cell Prolif. 2014 Oct;47(5):406-15. doi: 10.1111/cpr.12119. Epub 2014 Jul 23.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / drug therapy
  • Adenocarcinoma / immunology*
  • Adenocarcinoma of Lung
  • Antineoplastic Agents / immunology
  • Antioxidants / pharmacology
  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Coculture Techniques
  • G1 Phase Cell Cycle Checkpoints / drug effects
  • Glutathione / biosynthesis
  • Humans
  • Immunomodulation / drug effects*
  • Leukocytes, Mononuclear / immunology*
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / immunology*
  • Melatonin / immunology*
  • Melatonin / pharmacology*
  • Oxidative Stress / drug effects

Substances

  • Antineoplastic Agents
  • Antioxidants
  • Glutathione
  • Melatonin