A series of thiosemicarbazone derivatives was prepared and their anti-tumor activity in vitro was tested.,The X-ray investigation performed for compounds T2, T3 and T5 confirmed the synthesis pathway and assumed molecular structures of analyzed thiosemicarbazones.,The conformational preferences of the thiosemicarbazone system were characterized using theoretical calculations by AM1 method.,Selected compounds were converted into complexes of Cu (II) ions.,The effect of complexing on anti-tumor activity has been investigated.,The copper(II) complexes, with Schiff bases T1, T10, T12, T13, and T16 have been synthesized and characterized by chemical and elemental analysis, FTIR spectroscopy and TGA method.,Thermal properties of coordination compounds were studied using TG-DTG techniques under dry air atmosphere.,G361, A375, and SK-MEL-28 human melanoma cells and BJ human normal fibroblast cells were treated with tested compounds and their cytotoxicity was evaluated with MTT test.,The compounds with the most promising anti-tumour activity were then selected and their cytotoxicity was verified with cell cycle analysis and apoptosis/necrosis detection.,Additionally, DNA damages in the form of a basic sites presence and the expression of oxidative stress and DNA damage response genes were evaluated.,The obtained results indicate that complexation of thiosemicarbazone derivatives with Cu (II) ions improves their antitumor activity against melanoma cells.,The observed cytotoxic effect is associated with DNA damage and G2/M phase of cell cycle arrest as well as disorders of the antioxidant enzymes expression.
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.