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

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.