Efeito antiproliferativo e pró-apoptótico de derivados de lausona em células de melanoma

• Ano de defesa: 2021
• Autor(a) principal: Franca, Mariana Nobre Farias de
• Orientador(a): Corrêa, Cristiane Bani
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Programa de Pós-Graduação: Pós-Graduação em Ciências da Saúde
• Palavras-chave em Português: Ciências da saúde; Melanoma; Célula tumoral; Lausona; Citotoxicidade; Apoptose
• Palavras-chave em Inglês: Health Sciences; Melanoma; Tumor cell; Lawsona; Cytotoxicity; Apoptosis
• Área do conhecimento CNPq: CIENCIAS DA SAUDE
• Link de acesso: http://ri.ufs.br/jspui/handle/riufs/16854

Cancer affects millions of people worldwide and is responsible for 8.8 million deaths per year. Among the skin-type cancer, melanoma is the most aggressive and it was responsible for more than 50.000 deaths in 2020. The impact caused by this disease reveals the importance of research for new molecules with more effective antitumor activity. Natural products are an important source of bioactive molecules, and lawsone, naphthoquinone widely studied, is an important source of molecules with cytotoxic activity. In this context, the study aimed to evaluate the cytotoxic effect of galactoside derivative of lausona in melanoma cells. For this, the degree of inhibition of cell proliferation (GI) of 16 lawsone derivatives was evaluated against three tumor cell lines: lung carcinoma (A549), melanoma (B16F10) and glioma (C6), by the Sulforrodamine B assay. Seven compounds (1, 9, 10, 11, 13, 14 and 15) showed a degree of inhibition greater than 75% in the three cells studied. According to the chemical characteristics of molecule 9, such as the presence of triazole ring and galactose, and the low IC50 (5.3 μM) obtained in 72 h of treatment, this molecule was selected for the next tests in the B16F10 cells. The clonogenic assay showed that the molecule reduced the formation of melanoma colonies. In addition, morphological changes of the melanoma lineage were observed by staing with DAPI and Faloidin/FITC. In this analysis, apoptotic changes were evidenced, in addition to cytoplasmic reduction with changes in the disposition of actin fibers, and loss of cellular conformation in relation to control. These results corroborate flow cytometry, in which showed apoptotic (Annexin positive) and necrosis (PI positive) cell were evaluated, with a percentage increase in apoptosis cells after treatment. The results presented in this work reveal an important active potential of compound 9, derived from lawsone, on tumor cells.