In silico screening of an in-house natural products database by targeting PI3K alpha and confirmatory bioassays led to the identification of wortmannolol (1) as a novel inhibitor of PI3K alpha. In vitro enzymological assay revealed that 1 showed specific inhibitory activity on PI3K alpha. Compound 1 inhibited PI3 K activation in a concentration-dependent manner. Inhibition of the PI3 K/AKT signaling pathway by 1 also led to apoptosis of MCF-7 cells and activation of the pro-apoptotic signals. Furthermore, 1 displayed potent anti-tumor activity in MCF-7 xenograft CB-17/SCID mice. Intraperitoneal injection of 5 mg/kg per bodyweight almost fully suppressed tumor growth within 14 days without gross toxicity. Importantly, PI3 K/AKT activation was suppressed in tumor tissues from 1-treated mice, which was consistent with delayed tumor growth.
基金：
National Natural Science Foundation of China [81803387, 81703580, 21702067]; Hubei Provincial Natural Science Foundation of China [2018CFB152]
第一作者单位：[1]Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Hosp, Dept Pharm, 1095 Jiefang Rd, Wuhan, Peoples R China
通讯作者：
推荐引用方式(GB/T 7714)：
He Yan,Sun Weiguang,Li Qin,et al.Wortmannolol Induces Breast Cancer Cell Death In Vitro and In Vivo by Targeting Phosphoinositide 3-Kinase α[J].CHEMISTRYSELECT.2020,5(7):2214-2218.doi:10.1002/slct.201904239.
APA：
He, Yan,Sun, Weiguang,Li, Qin,Zhu, Hucheng,Hu, Zhengxi&Zhang, Jinwen.(2020).Wortmannolol Induces Breast Cancer Cell Death In Vitro and In Vivo by Targeting Phosphoinositide 3-Kinase α.CHEMISTRYSELECT,5,(7)
MLA：
He, Yan,et al."Wortmannolol Induces Breast Cancer Cell Death In Vitro and In Vivo by Targeting Phosphoinositide 3-Kinase α".CHEMISTRYSELECT 5..7(2020):2214-2218
