Flavonoid extract Kushenol a exhibits anti‐proliferative activity in breast cancer cells via suppression of PI3K/AKT/mTOR pathway. (4th July 2022)

• Record Type: Journal Article
• Authors: Liu, Tao; Gong, Jinhua; Lai, Guobin; Yang, Yichao; Wu, Xiaoan; Wu, Xiuping
• Is Part Of: Cancer medicine. Volume 12:Number 2(2023)
• Page Start: 1643
• Page End: 1654
• Publication Date: 2022-07-04
• Subjects: apoptosis -- breast cancer -- Kushenol A -- PI3K/AKT/mTOR pathway -- proliferation; 616.994005
• DOI: 10.1002/cam4.4993
• Languages: English
• ISSNs: 2045-7634

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. Abstract : Kushenol A suppresses proliferation and induces apoptosis of breast cancer cells by inhibiting PI3K/AKT/mTOR signaling pathway. Kushenol A combined with PI3K inhibitor has a synergistic inhibitory effect on BC cell proliferation. Kushenol A is a potential therapeutic agent for breast cancer treatment.