Diosmin induce apoptosis through modulation of STAT-3 signaling in 7,12 dimethylbenz(a)anthracene induced harmster buccal pouch carcinogenesis
| Autor: | K.G. Suresh, K. Sivakumar, Muthusamy Rajasekar |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Male STAT3 Transcription Factor Carcinogenesis 9 10-Dimethyl-1 2-benzanthracene Diosmin DMBA Apoptosis medicine.disease_cause 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Cricetinae medicine Biomarkers Tumor Animals Caspase Cell Proliferation Pharmacology Mouth biology Neovascularization Pathologic Cell growth 7 12-Dimethylbenz[a]anthracene Body Weight General Medicine Cell biology 030104 developmental biology chemistry 030220 oncology & carcinogenesis Cancer research biology.protein Phosphorylation Mouth Neoplasms medicine.drug Signal Transduction |
| Zdroj: | Biomedicinepharmacotherapy = Biomedecinepharmacotherapie. 83 |
| ISSN: | 1950-6007 |
| Popis: | Diosmin is naturally found flavanoid in many citrus fruits known to have anti-inflammatory, antihyperglycemic, antioxidant and antimutagenic properties. Effects of Diosmin on IL-6/STAT-3 expression in hamster buccal pouch carcinogenesis remain unclear. Alterations in many genes encode crucial proteins, which regulate cell proliferation, differentiation and apoptosis have been implicated in oral cancer. In the present study, we investigated the effect of dietary Diosmin on IL-6/STAT-3 signaling in the 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch (HBP) carcinogenesis by examining the protein expression of IL-6/STAT-3 and its related genes. Immunoblotting and immunohistochemical analyses revealed that Diosmin (100mg/kgb.w) supplement inhibits key events in signaling especially STAT-3 phosphorylation and subsequent nuclear translocation. Results revealed that inhibition of proliferation and angiogenesis is associated with regulation of the STAT-3 pathway; where Diosmin prevents phosphorylation of JAK-1 which was ascend by IL-6, thereby inhibiting STAT-3 phosphorylation. Consequently, an imbalance in the Bax/Bcl-2 ratio triggered the caspase cascade in favor of apoptosis. Transmission electron microscopic studies proved the effect of Diosmin on ultrastructural changes. Finally our results provide significant evidence that Diosmin prevents the development and progression of HBP carcinomas through the inhibition of IL-6/STAT-3 signaling and its downstream events. Thus, Diosmin functions as a potent inhibitor of tumor development and progression by targeting IL-6/STAT-3 signaling may be an ideal candidate for cancer chemoprevention. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect