Resveratrol reduces IL-6 and VEGF secretion from co-cultured A549 lung cancer cells and adipose-derived mesenchymal stem cells

Tumour Biol. 2016 Jun;37(6):7573-82. doi: 10.1007/s13277-015-4643-0. Epub 2015 Dec 18.

Abstract

Stem cell therapies are important treatment methodologies used in many areas of experimental or clinical medicine. In recent studies of cancer models, Mesenchymal stem cells (MSCs) suppressed the growth of cancer cells. However, also in some studies, stem cell treatments have been shown to induce cancer formation, increase tumor volume, induce the formation of new vessels, and lead to cancer invasion. The presence of MSC-secreted cytokines and their effects on cancer cells limits the reliability of MSC-based treatments. Resveratrol (trans-3,5,4'-trihydroxystilbene), an antioxidant found in red wine, has been shown to have therapeutic effects against several cancers. The aim of this study was to co-culture MSCs with A549 cancer cells to suppress the release of cancer-promoting cytokines from MSCs and to increase the applicability and reliability of stem cell therapies with resveratrol. MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and neutral red cell viability assays were used to find safety dose of resveratrol. The MSCs secreted the cytokines IL-6 and VEGF, and the effect of resveratrol on these cytokines was analyzed by ELISA and western blot analysis of conditioned medium. One μM of resveratrol was found to be the safety dose for the A549 cancer cells and MSCs. We observed the highest release of IL-6 and VEGF from the co-cultured A549 cells and MSCs, and resveratrol was found to significantly decrease the release of these cytokines. Our study suggests that resveratrol exerts a positive effect on the release of cytokines. The safety dose of resveratrol can be administered together with stem cells during stem cell treatment.

Keywords: A549; Cancer cells; IL-6; Mesenchymal stem cells; VEGF and resveratrol.

MeSH terms

  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apoptosis / drug effects
  • Blotting, Western
  • Cell Proliferation / drug effects
  • Coculture Techniques
  • Culture Media, Conditioned / pharmacology*
  • Humans
  • Interleukin-6 / metabolism*
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / pathology
  • Mesenchymal Stem Cells / drug effects
  • Mesenchymal Stem Cells / metabolism*
  • Mesenchymal Stem Cells / pathology
  • Resveratrol
  • Stilbenes / pharmacology*
  • Tumor Cells, Cultured
  • Vascular Endothelial Growth Factor A / metabolism*

Substances

  • Antineoplastic Agents, Phytogenic
  • Culture Media, Conditioned
  • IL6 protein, human
  • Interleukin-6
  • Stilbenes
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Resveratrol