Reserpine inhibits DNA repair, cell proliferation, invasion and induces apoptosis in oral carcinogenesis via modulation of TGF-β signaling
| Autor: | Arun Kumar Ramu, Saud Alarifi, Bakrudeen Ali Ahmed Abdul, Daoud Ali, Mohamed Hussain Syed Abuthakir |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Male Reserpine DNA Repair DNA repair Carcinogenesis Poly ADP ribose polymerase 9 10-Dimethyl-1 2-benzanthracene Down-Regulation Apoptosis 030226 pharmacology & pharmacy General Biochemistry Genetics and Molecular Biology 03 medical and health sciences 0302 clinical medicine Transforming Growth Factor beta Cricetinae medicine Animals Neoplasm Invasiveness General Pharmacology Toxicology and Pharmaceutics Cell Proliferation Ku70 biology Chemistry Cell growth Mouth Mucosa General Medicine Cell biology Proliferating cell nuclear antigen Neoplasm Proteins Molecular Docking Simulation 030104 developmental biology biology.protein Mouth Neoplasms ERCC1 medicine.drug Signal Transduction |
| Zdroj: | Life sciences. 264 |
| ISSN: | 1879-0631 |
| Popis: | Reserpine is a natural indole alkaloid isolated from Rauwolfia serpentina and has potent antioxidant, antimicrobial, and anti-mutagenic properties. Accordingly, this study aimed to investigate the effect of reserpine on DNA repair, cell proliferation, invasion and apoptosis in 7,12-dimethylbenz[a]anthracene(DMBA)-induced hamster buccal pouch (HBP) carcinogenesis. Transforming growth factor-β (TGF-β) was found to induce Smad2, 3 and 4 phosphorylation triggering Smad3/Snail mediated DNA repair proteins and Smad2/4 nuclear translocation. In contrast, reserpine inhibits TGF-β dependent Smad2/3/4 phosphorylation, thereby blockage Smad3/Snail activation and Smad2/4 nuclear translocation. Interruption of these oncogenic signaling pathways leads to downregulating ERCC1, XPF, Ku70, DNA-PKcs, PCNA, cyclin D1, HIF-1α, IL-6, Mcl-1 and stimulates Bax, cytochrome C, Apaf-1, caspase-9, caspase-3 and PARP protein expressions. This study provides therapeutic potential of reserpine in inhibiting DNA repair, cell proliferation, and invasion while simultaneously inducing apoptosis via modulation TGF-β signals. |
| Databáze: | OpenAIRE |
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