Wortmannolol Induces Breast Cancer Cell Death In Vitro and In Vivo by Targeting Phosphoinositide 3-Kinase alpha

摘要

abstract_textpIn 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./p/abstract_text