RESUMO
Colorectal cancer (CRC) is notable for its high mortality and high metastatic characteristics. The shear force generated by bloodstream provides mechanical signals regulating multiple responses of cells, including metastatic cancer cells, dispersing in blood vessels. We, therefore, studied the effect of shear flow on circulating CRC cells in the present study. The CRC cell line SW620 was subjected to shear flow of 12.5 dynes/cm2 for 1 and 2 h separately. Resulting elevated caspase-9 and -3 indicated that shear flow initiated the apoptosis of SW620. Enlarged cell size associated with a higher level of cyclin D1 was coincident with the flow cytometric results indicating that the cell cycle was arrested at the G1 phase. An elevated phosphor-eNOSS1177 increased the production of nitric oxide and led to reactive oxygen species-mediated oxidative stress. Shear flow also regulated epithelial-mesenchymal transition (EMT) by increasing E-cadherin and ZO-1 while decreasing Snail and Twist1. The migration and invasion of sheared SW620 were also substantially decreased. Further investigations showed that mitochondrial membrane potential was significantly decreased, whereas mitochondrial mass and ATP production were not changed. In addition to the shear flow of 12.5 dynes/cm2, the expressions of EMT were compared at lower (6.25 dynes/cm2) and at higher (25 dynes/cm2) shear flow. The results showed that lower shear flow increased mesenchymal characteristics and higher shear flow increased epithelial characteristics. Shear flow reduces the malignancy of CRC in their metastatic dispersal that opens up new ways to improve cancer therapies by applying a mechanical shear flow device.
Assuntos
Apoptose , Movimento Celular , Neoplasias Colorretais , Transição Epitelial-Mesenquimal , Espécies Reativas de Oxigênio , Humanos , Neoplasias Colorretais/patologia , Neoplasias Colorretais/metabolismo , Linhagem Celular Tumoral , Espécies Reativas de Oxigênio/metabolismo , Estresse Mecânico , Potencial da Membrana Mitocondrial , Ciclina D1/metabolismo , Estresse Oxidativo , Caderinas/metabolismo , Óxido Nítrico/metabolismo , Caspase 9/metabolismo , Caspase 3/metabolismo , Proteína da Zônula de Oclusão-1/metabolismo , Proteína 1 Relacionada a Twist/metabolismoRESUMO
A series of ß-thioketiminate copper(I) complex trimers [LCuI]3 were synthesized by modifying the ligand framework with electron-withdrawing groups (F and Cl) or electron-donating groups (iPr and Me) at the N-aryl ring as well as with CF3 groups on the chelating backbone. This ligand modification significantly impacts the enhancement of Cuâ¯Cu short contacts, which can be rationalized by using steric and electronic factors of the chelated ligand. We observed that this intramolecular cuprophilicity among [LCuI]3 complexes is primarily governed by the size of N-aryl ortho-substituents. These findings were well supported by X-ray crystallography, Raman spectroscopy, and Mayer bond order analysis. The electronic effects induced by the ligand modification on the LCuI fragment were investigated using CO and 2,4,6-CNC6H2Me3 as probe molecules. Corroborated by the FTIR and CV measurements, our results reveal that the ß-thioketiminate SN chelators induce more pronounced changes in the electronic character of the LCuI fragment due to the presence of CF3 groups on the chelating backbone in comparison with the F or Cl substituents on the N-aryl ring.
RESUMO
The Ru(II)-nitrite complex, Ru4, is explored to release nitric oxide (NO) under acidic conditions and selectively induce a cytotoxic effect towards SK-MEL-28 cisplatin-resistant malignant melanoma cells. These findings suggest that targeting the tumor-associated pHe level could be an effective strategy for the drug function of Ru(II)-nitrite compounds.