Wortmannolol Induces Breast Cancer Cell Death In Vitro and In Vivo by Targeting Phosphoinositide 3‐Kinase α

In silico screening of an in‐house natural products database by targeting PI3K α and confirmatory bioassays led to the identification of wortmannolol ( 1 ) as a novel inhibitor of PI3K α . In vitro enzymological assay revealed that 1 showed specific inhibitory activity on PI3K α . 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.