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In vitro and computational studies showed that perezone inhibits PARP-1 and induces changes in the redox state of K562 cells.
Hernández-Rodríguez, Maricarmen; Mendoza Sánchez, Pablo I; Macias Perez, Martha Edith; Rosales Cruz, Erika; Mera Jiménez, Elvia; Nicolás Vázquez, María Inés; Miranda Ruvalcaba, René.
Afiliação
  • Hernández-Rodríguez M; Química inorgánica-orgánica del Departamento de Ciencias Químicas, de la Facultad de Estudios Superiores Cuautitlán Campo 1, Universidad Nacional Autónoma de México, Avenida 1o de Mayo S/N, Santa María las Torres, Cuautitlán Izcalli, Estado de México, Mexico.
  • Mendoza Sánchez PI; Química inorgánica-orgánica del Departamento de Ciencias Químicas, de la Facultad de Estudios Superiores Cuautitlán Campo 1, Universidad Nacional Autónoma de México, Avenida 1o de Mayo S/N, Santa María las Torres, Cuautitlán Izcalli, Estado de México, Mexico.
  • Macias Perez ME; Laboratorio de Cultivo Celular, Escuela Superior de Medicina, Instituto Politécnico Nacional, Salvador Díaz Mirón S/N, Santo Tomás, 11340 Ciudad de, Mexico.
  • Rosales Cruz E; Laboratorio de Hematopatologia, Escuela Nacional de Ciencias Biologicas, Instituto Politécnico Nacional, Prolongación de Carpio y Plan de Ayala s/n, Miguel Hidalgo, Santo Tomás, 11340 Ciudad de, Mexico.
  • Mera Jiménez E; Laboratorio de Cultivo Celular, Escuela Superior de Medicina, Instituto Politécnico Nacional, Salvador Díaz Mirón S/N, Santo Tomás, 11340 Ciudad de, Mexico.
  • Nicolás Vázquez MI; Química inorgánica-orgánica del Departamento de Ciencias Químicas, de la Facultad de Estudios Superiores Cuautitlán Campo 1, Universidad Nacional Autónoma de México, Avenida 1o de Mayo S/N, Santa María las Torres, Cuautitlán Izcalli, Estado de México, Mexico. Electronic address: nicovain@yahoo.com.m
  • Miranda Ruvalcaba R; Química inorgánica-orgánica del Departamento de Ciencias Químicas, de la Facultad de Estudios Superiores Cuautitlán Campo 1, Universidad Nacional Autónoma de México, Avenida 1o de Mayo S/N, Santa María las Torres, Cuautitlán Izcalli, Estado de México, Mexico. Electronic address: mirruv@yahoo.com.mx.
Arch Biochem Biophys ; 671: 225-234, 2019 08 15.
Article em En | MEDLINE | ID: mdl-31063714
Cancer is one of the leading causes of morbidity and mortality worldwide. This disease is characterized by uncontrolled growth and proliferation of abnormal cells with a high probability to develop metastasis. Recently, it was demonstrated that perezone, a sesquiterpene quinone, is capable to induce cell death in leukemia (K562), prostate (PC-3), colorectal (HCT-15) and lung (SKLU-1) cancer cell lines; however, its mechanism of action is unknown. Therefore, in this study, in vitro and computational studies were performed to determine the mechanism of action of perezone. Firstly, changes in K562 cell viability, as well as changes in the redox status of the cell in response to treatment with several concentrations of perezone were analyzed. The type of cell death induced, and the modification of the cell cycle were determined. In addition, MD simulations and docking studies were performed to investigate the interaction of perezone with seven regulators of the apoptotic process. Finally, the ability of perezone to inhibit PARP-1 was evaluated by in vitro studies. K562 cells treated with perezone exhibited decreased viability and more oxidized status, being this effect concentration-dependent. In addition, the increase of G0/G1 phase of cell cycle and apoptosis were observed. According to the performed computational studies conducted, perezone showed the highest affinity to PARP-1 enzyme being this complex the most stable due to the presence of a small and deep cavity in the active site, which allows perezone to fit deeply by forming hydrogen bonds and hydrophobic interactions, which drive this interaction. The activity of perezone as PARP-1 inhibitor was corroborated with an IC50 = 181.5 µM. The pro-apoptotic action of perezone may be related to PARP-1 inhibition and changes in the redox state of the cell. The obtained results allowed to understand the biological effect of perezone and, consequently, these could be employed to develop novel PARP-1 inhibitors.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Oxirredução / Sesquiterpenos / Inibidores de Poli(ADP-Ribose) Polimerases / Poli(ADP-Ribose) Polimerase-1 Limite: Humans Idioma: En Revista: Arch Biochem Biophys Ano de publicação: 2019 Tipo de documento: Article País de afiliação: México País de publicação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Oxirredução / Sesquiterpenos / Inibidores de Poli(ADP-Ribose) Polimerases / Poli(ADP-Ribose) Polimerase-1 Limite: Humans Idioma: En Revista: Arch Biochem Biophys Ano de publicação: 2019 Tipo de documento: Article País de afiliação: México País de publicação: Estados Unidos