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

Autor:	Moura AF; Departamento de Fisiologia e Farmacologia, Núcleo de Pesquisa e Desenvolvimento de Medicamentos - NPDM, Universidade Federal do Ceará, Fortaleza, CE, Brazil., de Castro MRC; Instituto de Química, Universidade Federal de Goiás, Goiânia, GO, Brazil., Naves RF; Instituto de Química, Universidade Federal de Goiás, Goiânia, GO, Brazil.; Instituto Federal de Goiás, Campus Inhumas, Inhumas, GO, Brazil., Araújo AJ; Departamento de Biotecnologia, Universidade Federal do Delta do Parnaíba, Parnaíba, PI, Brazil., Dos Santos MCL; Departamento de Fisiologia e Farmacologia, Núcleo de Pesquisa e Desenvolvimento de Medicamentos - NPDM, Universidade Federal do Ceará, Fortaleza, CE, Brazil., Filho JDBM; Departamento de Biotecnologia, Universidade Federal do Delta do Parnaíba, Parnaíba, PI, Brazil., Noda-Perez C; Instituto de Química, Universidade Federal de Goiás, Goiânia, GO, Brazil., Terra Martins F; Instituto de Química, Universidade Federal de Goiás, Goiânia, GO, Brazil., do O Pessoa C; Departamento de Fisiologia e Farmacologia, Núcleo de Pesquisa e Desenvolvimento de Medicamentos - NPDM, Universidade Federal do Ceará, Fortaleza, CE, Brazil., Filho MOM; Departamento de Fisiologia e Farmacologia, Núcleo de Pesquisa e Desenvolvimento de Medicamentos - NPDM, Universidade Federal do Ceará, Fortaleza, CE, Brazil.
Jazyk:	angličtina
Zdroj:	Anti-cancer agents in medicinal chemistry [Anticancer Agents Med Chem] 2022; Vol. 22 (12), pp. 2340-2351.
DOI:	10.2174/1871520621666211213092121
Abstrakt:	Background: New chalcones have been developed from the insertion of organic groups, among them sulfonamides, presenting varied biological activity. 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). 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. 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. 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. (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)
Databáze:	MEDLINE
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