Dauricine inhibits proliferation and promotes death of melanoma cells via inhibition of Src/ STAT3 signaling
| Autor: | Yu-Ting Wu, Wen-jun Ding, Bo Deng, En-Xin Zhang, Jingzhi Zhang, Xiao-li Jiang, Jun Kan, Zhang-Bin Tan, Bin Liu, Min Cai, You-cai Xu, Sui-hui Deng, Shuangwei Zhang, Rui-xue Chen |
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| Rok vydání: | 2021 |
| Předmět: |
STAT3 Transcription Factor
Programmed cell death Proto-Oncogene Proteins pp60(c-src) Apoptosis Benzylisoquinolines 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Cell Line Tumor Tetrahydroisoquinolines medicine Humans Cytotoxic T cell Phosphorylation STAT3 Melanoma Cell Proliferation Pharmacology 0303 health sciences biology Chemistry 030302 biochemistry & molecular biology medicine.disease Dauricine Molecular Docking Simulation Protein kinase domain 030220 oncology & carcinogenesis STAT protein biology.protein Cancer research Signal Transduction Proto-oncogene tyrosine-protein kinase Src |
| Zdroj: | Phytotherapy Research. 35:3836-3847 |
| ISSN: | 1099-1573 0951-418X |
| Popis: | Melanoma is the most common type of skin cancer. Signal transducer and activator of transcription 3 (STAT3) signaling has been demonstrated to be a therapeutic target for melanoma. Dauricine (Dau), an alkaloid compound isolated from the root of Menispermum dauricum DC., has shown tumor-suppressing effects in multiple human cancers, but its potential in melanoma remains unexplored. In this study, we demonstrated that Dau significantly inhibited the viability and proliferation of A375 and A2058 melanoma cells. Death of melanoma cells was also markedly promoted by Dau. Moreover, Dau inhibited phosphorylation-mediated activation of STAT3 and Src in a dose-dependent manner. Notably, constitutive activation of Src partially abolished the antiproliferative and cytotoxic activities of Dau on melanoma cells. Molecular docking showed that Dau could dock on the kinase domain of Src with a binding energy of -10.42 kcal/mol. Molecular dynamics simulations showed that Src-Dau binding was stable. Surface plasmon resonance imaging analysis also showed that Dau has a strong binding affinity to Src. In addition, Dau suppressed the growth of melanoma cells and downregulated the activation of Src/STAT3 in a xenograft model in vivo. These data demonstrated that Dau inhibits proliferation and promotes cell death in melanoma cells by inhibiting the Src/STAT3 pathways. |
| Databáze: | OpenAIRE |
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