Flavonoid extract Kushenol a exhibits anti-proliferative activity in breast cancer cells via suppression of PI3K/AKT/mTOR pathway

黄酮类提取物苦参醇 a 通过抑制 PI3K/AKT/mTOR 通路在乳腺癌细胞中表现出抗增殖活性

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作者:Tao Liu, Jinhua Gong, Guobin Lai, Yichao Yang, Xiaoan Wu, Xiuping Wu

Background

Kushenol A is natural flavonoid extract discovered in recent years, with potential anti-tumor activity. Its role in breast cancer is poorly understood.

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.

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.

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