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Cancer Med ; 12(2): 1643-1654, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-35789211

RESUMO

BACKGROUND: Kushenol A is natural flavonoid extract discovered in recent years, with potential anti-tumor activity. Its role in breast cancer is poorly understood. METHODS: To investigate biological function of Kushenol A in breast cancer (BC), Cell Counting Kit-8 assay, colony formation assay, flow cytometry, western blotting, qPCR analysis, and xenograft mouse model were performed. RESULTS: We found that Kushenol A treatment reduced proliferative capability and induced G0/G1 phase cell cycle arrest and apoptosis of BC cells in a concentration-dependent manner. Besides, Kushenol A treatment contributed to the upregulation of apoptosis-related and cell cycle-associated genes. In nude mice, Kushenol A administration repressed BC xenograft tumor growth. Mechanistically, phosphorylation levels of AKT and mTOR were markedly attenuated in Kushenol A-treated BC cells; however, there were no significant differences in total AKT and mTOR expressions. Moreover, PI3K inhibitor combined with Kushenol A exhibited synergistic inhibitory activity on cell proliferation. CONCLUSIONS: Taken together, our findings suggested that Kushenol A suppressed BC cell proliferation by modulating PI3K/AKT/mTOR signaling pathway. Kushenol A may be a promising therapeutic drug for treating BC.


Assuntos
Neoplasias da Mama , Proteínas Proto-Oncogênicas c-akt , Humanos , Animais , Camundongos , Feminino , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Camundongos Nus , Serina-Treonina Quinases TOR/metabolismo , Flavonoides/farmacologia , Neoplasias da Mama/patologia , Apoptose , Proliferação de Células , Linhagem Celular Tumoral
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