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

Abstract

In silico screening of an in‐house natural products database by targeting PI3Kα and confirmatory bioassays led to the identification of wortmannolol (1) as a novel inhibitor of PI3Kα. In vitro enzymological assay revealed that 1 showed specific inhibitory activity on PI3Kα. 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.