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

Abstract

Abstract 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.

Keywords

• apoptosis
• breast cancer
• Kushenol A
• PI3K/AKT/mTOR pathway
• proliferation