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Dauricine inhibits proliferation and promotes death of melanoma cells via inhibition of Src/ STAT3 signaling
Author(s) -
Deng Bo,
Jiang XiaoLi,
Tan ZhangBin,
Cai Min,
Deng SuiHui,
Ding WenJun,
Xu YouCai,
Wu YuTing,
Zhang ShuangWei,
Chen RuiXue,
Kan Jun,
Zhang EnXin,
Liu Bin,
Zhang JingZhi
Publication year - 2021
Publication title -
phytotherapy research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.019
H-Index - 129
eISSN - 1099-1573
pISSN - 0951-418X
DOI - 10.1002/ptr.7089
Subject(s) - stat3 , melanoma , proto oncogene tyrosine protein kinase src , stat protein , activator (genetics) , cancer research , src family kinase , cell growth , cancer cell , signal transduction , chemistry , microbiology and biotechnology , biology , cancer , biochemistry , receptor , genetics
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.