1. Diosmin induce apoptosis through modulation of STAT-3 signaling in 7,12 dimethylbenz(a)anthracene induced harmster buccal pouch carcinogenesis.
- Author
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Rajasekar M, Suresh K, and Sivakumar K
- Subjects
- 9,10-Dimethyl-1,2-benzanthracene, Animals, Biomarkers, Tumor metabolism, Body Weight drug effects, Cell Proliferation drug effects, Cricetinae, Diosmin therapeutic use, Male, Mouth pathology, Mouth ultrastructure, Mouth Neoplasms blood supply, Mouth Neoplasms ultrastructure, Neovascularization, Pathologic drug therapy, Neovascularization, Pathologic pathology, Apoptosis drug effects, Carcinogenesis pathology, Diosmin pharmacology, Mouth Neoplasms metabolism, Mouth Neoplasms pathology, STAT3 Transcription Factor metabolism, Signal Transduction drug effects
- Abstract
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., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)
- Published
- 2016
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