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HOI-02 induces apoptosis and G2-M arrest in esophageal cancer mediated by ROS
- Source :
- Cell Death & Disease
- Publication Year :
- 2015
- Publisher :
- Springer Science and Business Media LLC, 2015.
-
Abstract
- Reactive oxygen species (ROS) are chemically reactive molecules that perform essential functions in living organisms. Accumulating evidence suggests that many types of cancer cells exhibit elevated levels of ROS. Conversely, generation of ROS has become an effective method to kill cancer cells. (E)-3-hydroxy-3-(4-(4-nitrophenyl)-2-oxobut-3-en-1-yl) indolin-2-one, which is an NO2 group-containing compound designated herein as HOI-02, generated ROS and, in a dose-dependent manner, decreased esophageal cancer cell viability and inhibited anchorage-independent growth, followed by apoptosis and G2-M arrest. Moreover, results of an in vivo study using a patient-derived xenograft mouse model showed that HOI-02 treatment suppressed the growth of esophageal tumors, without affecting the body weight of mice. The expression of Ki-67 was significantly decreased with HOI-02 treatment. In addition, the phosphorylation of c-Jun, and expression of p21, cleaved caspase 3, and DCFH-DA were increased in the HOI-02-treated group compared with the untreated control group. In contrast, treatment of cells with (E)-3-(4-(4-aminophenyl)-2-oxobut-3-en-1-yl)-3-hydroxyindolin-2-one, which is an NH2 group-containing compound designated herein as HOI-11, had no effect. Overall, we identified HOI-02 as an effective NO2 group-containing compound that was an effective therapeutic or preventive agent against esophageal cancer cell growth.
- Subjects :
- Cyclin-Dependent Kinase Inhibitor p21
Male
Cancer Research
Programmed cell death
Indoles
Esophageal Neoplasms
Cell Survival
Immunology
Antineoplastic Agents
Apoptosis
Caspase 3
Mice, SCID
Biology
Cellular and Molecular Neuroscience
Cell Line, Tumor
Animals
Humans
Viability assay
Nitrobenzenes
Cell Proliferation
chemistry.chemical_classification
Reactive oxygen species
Cell growth
Cell Biology
Middle Aged
Xenograft Model Antitumor Assays
Tumor Burden
3. Good health
G2 Phase Cell Cycle Checkpoints
Transcription Factor AP-1
chemistry
Cell culture
Cancer cell
Cancer research
Original Article
Reactive Oxygen Species
Signal Transduction
Subjects
Details
- ISSN :
- 20414889
- Volume :
- 6
- Database :
- OpenAIRE
- Journal :
- Cell Death & Disease
- Accession number :
- edsair.doi.dedup.....2d54b6b47a81eddd945d8bdcf75f7b9c