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 ◽  
...  

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). Method: 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.

2008 ◽  
Vol 120 (3) ◽  
pp. 394-401 ◽  
Author(s):  
Shih-Chung Hsu ◽  
Chien-Chih Ou ◽  
Jhy-Wei Li ◽  
Tzu-Chao Chuang ◽  
Han-Pon Kuo ◽  
...  

2016 ◽  
Vol 48 (5) ◽  
pp. 537 ◽  
Author(s):  
AbdulrahmanK Al-Asmari ◽  
Anvarbatcha Riyasdeen ◽  
Rajamohamed Abbasmanthiri ◽  
Mohammed Arshaduddin ◽  
FahadAli Al-Harthi

2021 ◽  
Author(s):  
Jakeb SSM Petersen ◽  
Sarah Baird

Abstract Purpose: Anti-helmintic drugs mebendazole and albendazole are commonly used to treat a variety of parasitic infestations. They have recently shown some promising results in pre-clinical in vitro and in vivo anti-cancer studies. We compare their efficacy in breast and colon cancer cell lines as well as in non-cancerous cells and elucidate their mechanism of action. Methods: The drugs were screened for cytotoxicity in MDA-MB-231, MCF-7 (breast cancer), HT-29 (colorectal cancer) and mesenchymal stem cells, using the MTT assay. Their effects on the cell cycle, tubulin levels and cell death mechanisms were analysed using flow cytometry and fluorescent microscopy. Results: Mebendazole and albendazole were found to selectively kill cancer cells, being most potent in the colorectal cancer cell line HT-29, with both drugs having IC50 values of less than 1 µM at 48 hours. Both mebendazole and albendazole induced classical apoptosis characterised by caspase-3 activation, phosphatidylserine exposure, DNA fragmentation, mitochondrial membrane permeability and reactive oxygen species production. Cell cycle arrest in the G2/M phase was found, and tubulin polymerisation was disrupted.Conclusion: Mebendazole and albendazole cause selective cancer cell death via a mechanism of classical apoptosis and cell cycle arrest, which involves the destabilisation of microtubules.


Life Sciences ◽  
2015 ◽  
Vol 143 ◽  
pp. 105-113 ◽  
Author(s):  
Surbala Laishram ◽  
Dinesh Singh Moirangthem ◽  
Jagat Chandra Borah ◽  
Bikas Chandra Pal ◽  
Pankaj Suman ◽  
...  

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Hoang Le Tuan Anh ◽  
Phuong Thao Tran ◽  
Do Thi Thao ◽  
Duong Thu Trang ◽  
Nguyen Hai Dang ◽  
...  

Degalactotigonin (1) and three other steroidal compounds solasodine (2), O-acetyl solasodine (3), and soladulcoside A (4) were isolated from the methanolic extract of Solanum nigrum, and their chemical structures were elucidated by spectroscopic analyses. The isolated compounds were evaluated for cytotoxic activity against human pancreatic cancer cell lines (PANC1 and MIA-PaCa2) and lung cancer cell lines (A549, NCI-H1975, and NCI-H1299). Only degalactotigonin (1) showed potent cytotoxicity against these cancer cell lines. Compound 1 induced apoptosis in PANC1 and A549 cells. Further study on its mechanism of action in PANC1 cells demonstrated that 1 significantly inhibited EGF-induced proliferation and migration in a concentration-dependent manner. Treatment of PANC1 cells with degalactotigonin induced cell cycle arrest at G0/G1 phase. Compound 1 induced downregulation of cyclin D1 and upregulation of p21 in a time- and concentration-dependent manner and inhibited EGF-induced phosphorylation of EGFR, as well as activation of EGFR downstream signaling molecules such as Akt and ERK.


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