New Synthetic Sulfonamide Chalcone Induced Cell Cycle Arrest and Cell Death in Colorectal Adenocarcinoma Metastatic Cells (SW-620)

Author(s):

Andréa Felinto Moura*, Mirian Rita Carrilho de Castro, Raquel Ferreira Naves, Ana Jérsia Araújo, Maria Claudia Luciano dos Santos, José Delano Barreto Marinho Filho, Caridad Noda-Perez, Felipe Terra Martins, Claudia do O Pessoa and Manoel Odorico Moraes Filho   Pages 2340 - 2351 ( 12 )

Abstract:

<p>Background: New chalcones have been developed from the insertion of organic groups, among them sulfonamides, presenting varied biological activity. <p> Objective: The aim of this work was to determine the antitumor potential of a new synthetic sulfonamide chalcone (SSC185) against a colorectal metastatic lymph node-derived colorectal cancer cell line (SW-620). <p> Methods: Synthesis and characterization, including crystallography, of SSC185 were performed. SSC185 showed a selective cytotoxic effect against colorectal cancer cell lines. Therefore, the cytotoxic effect of SSC185 against SW- 620 was further investigated. We used optical and fluorescence microscopy, flow cytometry and Western blot to determine the antitumor effects of SSC185. <p> Results: SSC185 induced cytotoxicity in SW-620 cells in a time and concentration-dependent manner. Cell cycle progression was disrupted, with increased G2/M cell number and consequent cell death, with morphological alterations associated with apoptosis and necrosis. Cell death was associated with the activation and cleavage of PARP, and with reduced expression of the pro-apoptotic Bax protein and caspase 8, depending on the SSC185 concentration tested. Expression of the necroptosis pathway proteins RIP and MLKL was also reduced. These proteins are phosphorylated during the process of necroptosis. <p> Conclusion: We suggest that the mechanism involved in the cytotoxic effect of SSC185 against SW-620 in vitro may be related to the induction of cell cycle arrest in the G2/M phase and cell death by apoptosis or necroptosis, depending on the concentration used.</p>

Keywords:

Synthesis, cytotoxicity, cell death, apoptosis, necroptosis, cancer.

Affiliation:

Departamento de Fisiologia e Farmacologia, Núcleo de Pesquisa e Desenvolvimento de Medicamentos – NPDM, Universidade Federal do Ceará, Fortaleza, CE, Instituto de Química, Universidade Federal de Goiás, Goiânia, GO, Instituto de Química, Universidade Federal de Goiás, Goiânia, GO, Universidade Federal do Delta do Parnaíba, Parnaíba, PI, Departamento de Fisiologia e Farmacologia, Núcleo de Pesquisa e Desenvolvimento de Medicamentos – NPDM, Universidade Federal do Ceará, Fortaleza, CE, Universidade Federal do Delta do Parnaíba, Parnaíba, PI, Instituto de Química, Universidade Federal de Goiás, Goiânia, GO, Brazil; dInstituto Federal de Goiás, Campus Inhumas, Inhumas, GO, Instituto de Química, Universidade Federal de Goiás, Goiânia, GO, Brazil; dInstituto Federal de Goiás, Campus Inhumas, Inhumas, GO, a Departamento de Fisiologia e Farmacologia, Núcleo de Pesquisa e Desenvolvimento de Medicamentos – NPDM, Universidade Federal do Ceará, Fortaleza, CE, Departamento de Fisiologia e Farmacologia, Núcleo de Pesquisa e Desenvolvimento de Medicamentos – NPDM, Universidade Federal do Ceará, Fortaleza, CE

Graphical Abstract:

Read Full-Text article