Please use this identifier to cite or link to this item: http://www.repositorio.ufop.br/handle/123456789/11076
Title: A novel platinum complex containing a piplartine derivative exhibits enhanced cytotoxicity, causes oxidative stress and triggers apoptotic cell death by ERK/p38 pathway in human acute promyelocytic leukemia HL-60 cells.
Authors: Oliveira, Maiara de Souza
Barbosa, Marília Imaculada Frazão
Souza, Thiago Belarmino de
Moreira, Diogo Rodrigo de Magalhães
Martins, Felipe Terra
Villarreal, Wilmer
Machado, Rafael Pereira
Doriguetto, Antônio Carlos
Soares, Milena Botelho Pereira
Bezerra, Daniel Pereira
Keywords: Piperlongumine
Apoptosis
ROS
Issue Date: 2019
Citation: OLIVEIRA, M. de S. et al. A novel platinum complex containing a piplartine derivative exhibits enhanced cytotoxicity, causes oxidative stress and triggers apoptotic cell death by ERK/p38 pathway in human acute promyelocytic leukemia HL-60 cells. Redox Biology, v. 20, p. 182-194, jan. 2019. Disponível em: <https://www.sciencedirect.com/science/article/pii/S2213231718305512?via%3Dihub>. Acesso em: 7 mar. 2019.
Abstract: Piplartine (piperlongumine) is a plant-derived compound found in some Piper species that became a novel potential antineoplastic agent. In the present study, we synthesized a novel platinum complex containing a piplartine derivative cis-[PtCl(PIP-OH)(PPh3)2]PF6 (where, PIP-OH = piplartine demethylated derivative; and PPh3 = triphenylphosphine) with enhanced cytotoxicity in different cancer cells, and investigated its apoptotic action in human promyelocytic leukemia HL-60 cells. The structure of PIP-OH ligand was characterized by X-ray crystallographic analysis and the resulting platinum complex was characterized by infrared, molar conductance measurements, elemental analysis and NMR experiments. We found that the complex is more potent than piplartine in a panel of cancer cell lines. Apoptotic cell morphology, increased internucleosomal DNA fragmentation, without cell membrane permeability, loss of the mitochondrial transmembrane potential, increased phosphatidylserine externalization and caspase-3 activation were observed in complex-treated HL-60 cells. Treatment with the complex also caused a marked increase in the production of reactive oxygen species (ROS), and the pretreatment with N-acetyl-L-cysteine, an antioxidant, reduced the complex-induced apoptosis, indicating activation of ROS-mediated apoptosis pathway. Important, pretreatment with a p38 MAPK inhibitor (PD 169316) and MEK inhibitor (U-0126), known to inhibit ERK1/2 activation, also prevented the complex-induced apoptosis. The complex did not induce DNA intercalation in cell-free DNA assays. In conclusion, the complex exhibits more potent cytotoxicity than piplartine in a panel of different cancer cells and triggers ROS/ERK/p38-mediated apoptosis in HL-60 cells.
URI: http://www.repositorio.ufop.br/handle/123456789/11076
ISSN: 2213-2317
metadata.dc.rights.license: This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Fonte: o próprio artigo.
Appears in Collections:DEFAR - Artigos publicados em periódicos

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