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Indolyl-chalcone derivatives induce hepatocellular carcinoma cells apoptosis through oxidative stress related mitochondrial pathway in vitro and in vivo.
- Source :
-
Chemico-Biological Interactions . Sep2018, Vol. 293, p61-69. 9p. - Publication Year :
- 2018
-
Abstract
- Abstract A facile method of assembling oxindole and phthalide units through a Lewis based catalyzed allylic alkylation reaction of Morita–Baylis–Hillman carbonates of isatins and 3-cyanophthalides was recently developed. The method efficiently delivers a hybrid of 3,3′-disubstituted oxindole with a valuable phthalide pharmacophore. In the present study, we proved the deleterious effects of 5h2c, a screened synthesis compound, against hepatocellular carcinoma (HCC) in both in vitro and in vivo models. 5h2c strongly decreased cell viability, caused over-release of lactate dehydrogenase, inhibited cell migration, and enhanced the apoptosis rate in HepG2 and PLC/PRF/5 cells. 5h2c led to an increase in intracellular reactive oxygen species levels and a decrease in mitochondrial membrane potential. In HepG2-and PLC/PRF/5-xenograft tumor mouse models, treatment with 5h2c inhibited tumor growth without affecting the animals' bodyweight or organ functions. Proteome profiling of tumor tissues after 24-h exposure to 5h2c showed significantly enhanced expression levels of Bcl-2 associated X protein, cleaved caspase −3, −8, and −9, nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), heme oxygenase-2, paraoxonase 2, catalase, and factor associated suicide ligand, and reduced the expression levels of B-cell lymphoma-2, B-cell lymphoma-extra large, heat shock protein 27, heat shock protein 60, and heat shock protein 70 in HepG2 and PLC/PRF/5 cells. All of our data confirmed that oxidative stress-mediated mitochondrial apoptosis (especially the Nrf-2/HO-1 pathway) is responsible for 5h2c-induced HCC damage. Highlights • 5h2c is a compound of 3,3′-disubstituted oxindole with a phthalide pharmacophore. • 5h2c induces apoptosis in hepatocellular carcinoma cells. • 5h2c inhibited the growth of HepG2-and PLC/PRF/5-xenografted tumor in mice. • 5h2c-induced apoptosis via oxidative stress-mediated mitochondrial function. • 5h2c promotes apoptosis of HCC cells through Nrf-2/HO-1 pathway. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00092797
- Volume :
- 293
- Database :
- Academic Search Index
- Journal :
- Chemico-Biological Interactions
- Publication Type :
- Academic Journal
- Accession number :
- 131795454
- Full Text :
- https://doi.org/10.1016/j.cbi.2018.07.025