Oxidative stress-mediated intrinsic apoptosis in human promyelocytic leukemia HL-60 cells induced by organic arsenicals
| Autor: | Hui-Min Zhong, Xin-You Chen, Yi Liu, Feng-Lei Jiang, Yu-Jiao Liu, Xiao-Yang Fan |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Acute promyelocytic leukemia Apoptosis HL-60 Cells medicine.disease_cause Arsenicals Article 03 medical and health sciences chemistry.chemical_compound Arsenic Trioxide Leukemia Promyelocytic Acute medicine Humans Arsenic trioxide Cell Proliferation chemistry.chemical_classification Membrane Potential Mitochondrial Reactive oxygen species Multidisciplinary biology Caspase 3 Cytochrome c Intrinsic apoptosis Cytochromes c Oxides Glutathione medicine.disease Gene Expression Regulation Neoplastic Oxidative Stress 030104 developmental biology chemistry Biochemistry biology.protein MCF-7 Cells Reactive Oxygen Species Oxidative stress Signal Transduction |
| Zdroj: | Scientific Reports |
| ISSN: | 2045-2322 |
| Popis: | Arsenic trioxide has shown the excellent therapeutic efficiency for acute promyelocytic leukemia. Nowadays, more and more research focuses on the design of the arsenic drugs, especially organic arsenicals, and on the mechanism of the inducing cell death. Here we have synthesized some organic arsenicals with Schiff base structure, which showed a better antitumor activity for three different kinds of cancer cell lines, namely HL-60, SGC 7901 and MCF-7. Compound 2a (2-(((4-(oxoarsanyl)phenyl)imino)methyl)phenol) and 2b (2-methoxy-4-(((4-(oxoarsanyl)phenyl)imino)methyl)phenol) were chosen for further mechanism study due to their best inhibitory activities for HL-60 cells, of which the half inhibitory concentration (IC50) were 0.77 μM and 0.51 μM, respectively. It was illustrated that 2a or 2b primarily induced the elevation of reactive oxygen species, decrease of glutathione level, collapse of mitochondrial membrane potential, release of cytochrome c, activation of Caspase-3 and apoptosis, whereas all of the phenomena can be eliminated by the addition of antioxidants. Therefore, we concluded that compound 2a and 2b can induce the oxidative stress-mediated intrinsic apoptosis in HL-60 cells. Both the simplicity of structure with Schiff base group and the better anticancer efficiency demonstrate that organic arsenicals are worthy of further exploration as a class of potent antitumor drugs. |
| Databáze: | OpenAIRE |
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