Resveratrol, a dietary product present in grapes, vegetables and berries, regulates several signaling pathways that control cell division, cell growth, apoptosis and metastasis. Malignant melanoma proliferates more readily in comparison with any other types of skin cancer. In the present study, the anti-cancer effect of resveratrol on melanoma cell proliferation was evaluated. Treating A375SM cells with resveratrol resulted in a decrease in cell growth. The alteration in the levels of cell cycle-associated proteins was also examined by western blot analysis. Treatment with resveratrol was observed to increase the gene expression levels of p21 and p27, as well as decrease the gene expression of cyclin B. In addition, the generation of reactive oxygen species (ROS) and endoplasmic reticulum (ER) stress were confirmed at the cellular and protein levels using a 2′,7′-dichlorofluorescein diacetate assay, TUNEL assay and western blot analysis. Resveratrol induced the ROS-p38-p53 pathway by increasing the gene expression of phosphorylated p38 mitogen-activated protein kinase, while it induced the p53 and ER stress pathway by increasing the gene expression levels of phosphorylated eukaryotic initiation factor 2α and C/EBP homologous protein. The enhanced ROS-p38-p53 and ER stress pathways promoted apoptosis by downregulating B-cell lymphoma-2 (Bcl-2) expression and upregulating Bcl-2-associated X protein expression. In conclusion, resveratrol appears to be an inducer of ROS generation and ER stress, and may be responsible for growth inhibition and cell cycle arrest of A375SM melanoma cells.

Short-term serious outcomes strongly correlated with the etiology assigned in the ED visit. The importance of the physician's clinical judgment should be further studied to determine if it should become incorporated in risk-stratification tools for prognostication and safe management of ED syncope patients.

Although the effects of stem cells expressing anticancer genes on tumor growth have been demonstrated by many researchers in various types of cancer, relatively few studies have investigated their inhibitory effects on cancer metastasis. In the present study, we examined the inhibitory effects of cytosine deaminase (CD)/5-fluorocytosine (5-FC) and interferon-β (IFN-β) using genetically engineered neural stem cells (hNSCs) in a cellular and metastasis model of renal cell carcinoma (RCC). The CD/5-FC method has the advantage of minimizing damage to normal tissues since it selectively targets cancer cells by the CD gene, which converts prodrug 5-FC to the drug 5-fluorouracil. Moreover, we used hNSCs as a tool to effectively deliver the anticancer genes to the tumor site. These stem cells are known to possess tumor-tropism because of chemoattractant factors expressed in cancer cells. Therefore, we ascertained the expression of these factors in A498 cells, a cell line of RCC, and identified the A498-specific migration ability of hNSCs. We also confirmed that the proliferation of A498 cells was significantly reduced by therapeutic hNSCs in the presence of 5-FC. Furthermore, we established an A498 metastasis model. In the animal experiment, the weight of the lungs increased in response to cancer metastasis, but was normalized by hNSCs expressing CD and/or IFN-β genes, while the incidence of liver metastasis was suppressed by the hNSCs. Overall, the results of this study demonstrate that stem cells expressing anticancer genes have the potential for use as an alternative to conventional therapy for metastatic cancer.