坏死性下垂
细胞凋亡
细胞毒性T细胞
程序性细胞死亡
细胞周期
细胞毒性
细胞周期检查点
癌症研究
流式细胞术
细胞培养
生物
细胞生长
半胱氨酸蛋白酶
化学
分子生物学
细胞生物学
生物化学
体外
遗传学
作者
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 N. Pérez,Felipe Terra Martins,Cláudia Pessoa,Manoel Odorico Moraes Filho
标识
DOI:10.2174/1871520621666211213092121
摘要
New chalcones have been developed from the insertion of organic groups, among them sulfonamides, presenting varied biological activity.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).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.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.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.
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