Anti-proliferative and pro-apoptotic activity of glycosidic derivatives of lawsone in melanoma cancer cell

BMC Cancer

Jileno Ferreira Santos¹  Ricardo Scher¹  João Henrique Oliveira Bonifacio¹  Cristiane Bani Corrêa²  Edmilson Willian Propheta dos Santos²  Mariana Nobre Farias de Franca²  Waldecy de Lucca Junior³  Flaviano Melo Ottoni⁴  Ricardo José Alves⁴  Raquel Geralda Isidório⁴ 

[1] Laboratory of Biology and Immunology of Cancer and Leishmania, Department of Morphology, Federal University of Sergipe, São Cristóvão, Sergipe, Brasil;Laboratory of Biology and Immunology of Cancer and Leishmania, Department of Morphology, Federal University of Sergipe, São Cristóvão, Sergipe, Brasil;Graduate program in health sciences, Federal University of Sergipe, Aracaju, Sergipe, Brazil;Laboratory of Molecular Neuroscience of Sergipe, Department of Morphology, Federal University of Sergipe, São Cristóvão, Sergipe, Brazil;Laboratory of Pharmaceutical Chemistry, Department of Pharmaceutical Products, Faculty of Pharmacy, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil;

关键词: Lawsone;    Melanoma;    Cytotoxicity;    Apoptosis;    Flow cytometer;    Migration;    Clonogenic assay;   

DOI  :  10.1186/s12885-021-08404-4

来源: Springer

【 摘 要 】

BackgroundMelanoma is a malignant cancer that affects melanocytes and is considered the most aggressive skin-type cancer. The prevalence for melanoma cancer for the last five year is about one million cases. The impact caused of this and other types of cancer, revel the importance of research into potential active compounds. The natural products are an important source of compounds with biological activity and research with natural products may enable the discovery of compounds with potential activity in tumor cells.MethodsThe Sulforhodamine B was used to determine cell density after treatment with lawsone derivatives. Apoptosis and necrosis were analyzed by flow cytometer. Morphological changes were observed by fluorescence using the Phalloidin/FITC and DAPI stains. The clonogenic and wound healing assays were used to analyze reduction of colonies formation and migratory capacity of melanoma cells, respectability.ResultsIn pharmacological screening, seven compounds derived from lawsone were considered to have high cytotoxic activity (GI > 75%). Three compounds were selected to assess the inhibitory concentration for 50% of cells (IC50), and the compound 9, that has IC50 5.3 μM in melanoma cells, was selected for further analyses in this cell line. The clonogenic assay showed that the compound is capable of reducing the formation of melanoma colonies at 10.6 μM concentration. The compound induced apoptotic morphological changes in melanoma cells and increased by 50% the cells dying from apoptosis. Also, this compound reduced the migratory capacity of melanoma cells.ConclusionsThe results of this study showed that the evaluated lawsone derivatives have potential activity on tumor cells. The compound 9 is capable of inducing cell death by apoptosis in melanoma cells (B16F10).

【 授权许可】

CC BY