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

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.

Treatment with olopatadine and naphazoline hydrochloride reduces allergic conjunctivitis in mice through alterations in inflammation, NGF and VEGF

“…VEGF exerts a strong mitogenic effect on endothelial cells and is regarded as a vascular endothelial cell-specific mitogen, inducing the proliferation of vascular endothelial cells and promoting angiogenesis (51). The biological activity of VEGF depends on the expression levels, the distribution of the target cell receptors and its integration with the receptors (52). Previous studies have demonstrated that hypoxia results in the high expression of VEGF, and that the alteration in retinal microvascular permeability in diabetic retinopathy is associated with VEGF (52,53).…”

“…The biological activity of VEGF depends on the expression levels, the distribution of the target cell receptors and its integration with the receptors (52). Previous studies have demonstrated that hypoxia results in the high expression of VEGF, and that the alteration in retinal microvascular permeability in diabetic retinopathy is associated with VEGF (52,53). In addition, VEGF and the corresponding receptor are integrated, resulting in retinal endothelial cell proliferation, migration and contributing to the formation of new blood vessels which destroy the blood-retina shielding protection in retinal endothelial cells (54).…”

Liquid crystalline assembly for potential combinatorial chemo–herbal drug delivery to lung cancer cells

“…52 Moreover, the chemopreventive polyphenolic RSV was reported as antiangiogenic factor which reduces VEGF secretion from cocultured A549. 53 Thanks to the synergistic effect of our chemo-herbal combination (PMX-RSV), the developed nanocarriers succeeded to develop additional control for tumor growth. 27 These results were in agreement with CASP-3 level ( Figure 4D) that is activated in the apoptotic cells in which lungs treated with ion-paired PMX-RSV-LCNPs (F10) showed significantly higher active CASP-3 (2.8 ng/g tissue) than those treated with free PMX/RSV (1.9 ng/g tissue) (P,0.05).…”

Effects of resveratrol, curcumin, berberine and other nutraceuticals on aging, cancer development, cancer stem cells and microRNAs

“…RES has been shown to inhibit the secretion of IL-6 and VEGF from A549 lung cancer cells when they were co-cultured with adipose-derived mesenchymal stem cells [72]. …”