Baicalein Induces Caspase‐dependent Apoptosis Associated with the Generation of ROS and the Activation of AMPK in Human Lung Carcinoma A549 Cells

ABSTRACT Preclinical Research Baicalein is one of the main bioactive flavonoids found in the roots of Scutellaria baicalensis Georgi. Here, we report that baicalein‐induced growth inhibition was associated with the induction of apoptosis in human lung carcinoma A549 cells. Baicalein stimulated the expression of DR5, FasL, and FADD, and activated caspase‐8 by reducing the levels of FLIPs (FLICE‐inhibitory proteins). The apoptotic cell death was also connected with an activation of caspase‐9 and −3, and cleavage of poly(ADP‐ribose) polymerase; however, a blockage of caspase activation abolished baicalein‐induced apoptotic potentials. Additionally, baicalein caused a mitochondrial membrane potential (MMP), the truncation of Bid, and the translocation of pro‐apoptotic Bax to the mitochondria, thereby inducing the release of cytochrome c into the cytosol. In turn, baicalein increased the generation of reactive oxygen species (ROS); however, an ROS scavenger, N‐acetylcysteine, notably attenuated baicalein‐mediated loss of MMP and activation of caspases. Furthermore, baicalein activated the AMP‐activated protein kinase (AMPK) signaling pathway. Consequently, baicalein‐triggered cell death was attenuated by an AMPK inhibitor, but increased by an AMPK activator, compound C. Overall, the results suggest that the apoptotic activity of baicalein may be associated with caspase‐dependent cascade through the activation of both intrinsic and extrinsic signaling pathways connected with ROS generation and AMPK activation. Drug Dev Res 77 : 73–86, 2016. © 2016 Wiley Periodicals, Inc.