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Publication
The biological performance of purified supercoiled p53 plasmid DNA in different cancer cell lines
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Advisor(s)
Abstract(s)
Tumor suppressor p53 remains one of the most interesting therapeutic targets in cancer gene therapy due to its
consistent mutation in numerous cancers. Thus, the reinstatement of the p53 expression and function can be seen
as an effective alternative for cancer treatment, motivating research in this field. In this study, L-methionine
matrix was used to purify the supercoiled topoisoform of a plasmid DNA encoding the p53 protein. This pure
biopharmaceutical was conjugated with liposomes to comprehensively analyze its in vitro performance and
therapeutic potential in different cancer cell lines, including the lung and cervix models. A different profile of
cellular responses was attained after the transfection of these cancer cell lines with the p53-pDNA. Actually, the
in vitro transfection with pure sc p53-pDNA resulted in a higher expression of the tumor suppressor protein in
cancer 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 in
A549 lung cancer cells. Overall, our findings emphasize the potential of sc pDNA gene-based therapy, also
raising awareness of the need to adjust the therapeutics, considering the feature of high heterogeneity of cancer
cells.
Description
Keywords
Tumor suppressor p53 Supercoiled plasmid DNA Gene Therapy L-methionine chromatography
Citation
J.F.A. Valente, A. Sousa, V.M. Gaspar, J.A. Queiroz, F. Sousa, The biological performance of purified supercoiled p53 plasmid DNA in different cancer cell lines, Process Biochemistry, Volume 75, 2018, Pages 240-249, ISSN 1359-5113, https://doi.org/10.1016/j.procbio.2018.09.014
Publisher
Elsevier