The biological performance of purified supercoiled p53 plasmid DNA in different cancer cell lines

• Autor(a) principal: Valente, J. F. A.
• Data de Publicação: 2018
• Outros Autores: Sousa, A., Gaspar, V. M., Queiroz, João, Fani, Sousa
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10400.6/8183
• topic: Gene Therapy; L-methionine chromatography; Supercoiled plasmid DNA; Tumor suppressor p53

Tumor suppressor p53 remains one of the most interesting therapeutic targets in cancer gene therapy due to itsconsistent mutation in numerous cancers. Thus, the reinstatement of the p53 expression and function can be seenas an effective alternative for cancer treatment, motivating research in thisfield. In this study,L-methioninematrix was used to purify the supercoiled topoisoform of a plasmid DNA encoding the p53 protein. This purebiopharmaceutical was conjugated with liposomes to comprehensively analyze itsin vitroperformance andtherapeutic potential in different cancer cell lines, including the lung and cervix models. A different profile ofcellular responses was attained after the transfection of these cancer cell lines with the p53-pDNA. Actually, thein vitrotransfection with pure sc p53-pDNA resulted in a higher expression of the tumor suppressor protein incancer cells when compared with the native pDNA samples (oc + sc topoisoforms). Also, wild-type p53 ex-pression following transfection was significantly higher in HeLa cervix cancer cells compared to that obtained inA549 lung cancer cells. Overall, ourfindings emphasize the potential of sc pDNA gene-based therapy, alsoraising awareness of the need to adjust the therapeutics, considering the feature of high heterogeneity of cancer cells.