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Baicalein Induces Caspase‐dependent Apoptosis Associated with the Generation of ROS and the Activation of AMPK in Human Lung Carcinoma A549 Cells
Author(s) -
Kim Hong Jae,
Park Cheol,
Han MinHo,
Hong SuHyun,
Kim GiYoung,
Hoon Hong Sang,
Deuk Kim Nam,
Choi Yung Hyun
Publication year - 2016
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.21298
Subject(s) - baicalein , scutellaria baicalensis , ampk , chemistry , apoptosis , cytochrome c , microbiology and biotechnology , fadd , caspase , reactive oxygen species , signal transduction , programmed cell death , protein kinase a , pharmacology , kinase , biochemistry , biology , medicine , alternative medicine , pathology , traditional chinese medicine
Preclinical ResearchBaicalein 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.